Early embryogenesis of Caenorhabditis elegans provides a striking example of the generation of polarity and the partitioning of cytoplasmic factors according to this polarity. Microfilaments (MFs) appear to play a critical role in these processes. By visualizing the distribution of MFs and by studying the consequences of disrupting MFs for short, defined periods during zygote development, we have generated some new ideas about when and how microfilaments function in the zygote.

Post‐transcriptional regulation faces a distinctive challenge in gametes. Transcription is limited when the germ cells enter the division phase due to condensed chromatin, while gene expression during gamete maturation, fertilization, and early cleavage depends on existing mRNA post‐transcriptional coordination. The dynamics of the 3ʹ‐poly(A) tail play crucial roles in defining mRNA fate. The 3ʹ‐poly(A) tail is covered with poly(A)‐binding proteins (PABPs) that help to mediate mRNA metabolism and recent work has shed light on the number and function of germ cell‐specific (...) expressed PABPs. There are two structurally different PABP groups distinguished by their cytoplasmic and nuclear localization. Both lack catalytic activity but are coupled with various roles through their interaction with multifunctional partners during mRNA metabolism. Here, we present a synopsis of PABP function during gametogenesis and early embryogenesis and describe both conventional and current models of the functions and regulation of PABPs, with an emphasis on the physiological significance of how germ cell‐specific PABPs potentially affect human fertility. (shrink)

Embryos and microscopes share a long, remarkable history and biologists have always been intrigued to watch how embryos develop under the microscope. Here we discuss the advances in microscopy which have greatly influenced our current understanding of embryogenesis. We highlight the evolution of microscopes and the optical technologies that have been instrumental in studying various developmental processes. These imaging modalities provide mechanistic insights into the dynamic cellular and molecular events which drive lineage commitment and morphogenetic changes in the developing (...) embryo. We begin the journey with a brief history of microscopy to study embryos. First, we review the principles and optics of light, fluorescence, confocal, and electron microscopy which have been key techniques for imaging cellular and molecular events during embryonic development. Next, we discuss recent key imaging modalities such as light‐sheet microscopy, which are suitable for whole embryo imaging. Further, we highlight imaging techniques like multiphoton and super resolution microscopy for beyond light diffraction limit, high resolution imaging. Lastly, we review some of the scattering‐based imaging methods and techniques used for imaging human embryos. (shrink)

In this essay, I attempt to provide answers to the following four queries concerning the metaphysics of early human embryogenesis. (1) Following its first cellular fission, is it coherent to claim that one and only one of two “blastomeric” twins of a human zygote is identical with that zygote? (2) Following the fusion of two human pre-embryos, is it coherent to claim that one and only one pre-fusion pre-embryo is identical with that postfusion pre-embryo? (3) Does a live human (...) being come into existence only when its brain comes into existence? (4) At implantation, does a pre-embryo become a mere part of its mother? I argue that either if things have quidditative properties or if criterialism is false, then queries (1) and (2) can be answered in the affirmative; that in light of recent developments in theories of human death and in light of a more “functional” theory of brains, query (3) can be answered in the negative; and that plausible mereological principles require a negative answer to query (4). (shrink)

Sex‐specific transcriptional and epigenomic profiles are detectable in the embryo very soon after fertilization. I propose that in male (XY) and female (XX) pre‐implantation embryos sex chromosomes establish sexually dimorphic interactions with the autosomes, before overt differences become apparent and long before gonadogenesis. Lineage determination restricts expression biases between the sexes, but the epigenetic differences are less constrained and can be perpetuated, accounting for dimorphisms that arise later in life. In this way, sexual identity is registered in the epigenome very (...) early in development. As development progresses, sex‐specific regulatory modules are harbored within shared transcriptional networks that delineate common traits. In reviewing this field, I propose that analyzing the mechanisms for sexual dimorphisms at the molecular and biochemical level and incorporating developmental and environmental factors will lead to a greater understanding of sex differences in health and disease. (shrink)

Comparative analysis of nematode development has revealed considerable variations in how the fates of embryonic cells are specified. Such early variations seem enigmatic as they do not influence the resultant structure or performance of the emerging animal. Three different nematode species are used to consider why alternative ways to reach the same goal may have been established during evolution and why early steps of embryogenesis are particularly variable. A scenario is sketched with a shift from late to early cell (...) specification, along with an increase in maternal contribution and developmental tempo and a decrease in regulative potential expressing different developmental strategies. Future studies of larger numbers of species are needed to assess the extent of such variations and to understand more fully the under lying mechanisms, rules and driving forces. BioEssays 23:841–847, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

In addressing bioethical issues at the beginning of human life, such as abortion, in vitro fertilization, and embryonic stem cell research, one primary concern regards establishing when a developing human embryo or fetus can be considered a person. Thomas Aquinas argues that an embryo or fetus is not a human person until its body is informed by a rational soul. Aquinas's explicit account of human embryogenesis has been generally rejected by contemporary scholars due to its dependence upon medieval biological (...) data, which has been far surpassed by current scientific research. A number of scholars, however, have attempted to combine Aquinas's basic metaphysical account of human nature with current embryological data to develop a contemporary Thomistic account of a human person's beginning. In this article, I discuss two recent interpretations in which it is argued that a human person does not begin to exist until a fetus has developed a functioning cerebral cortex. (shrink)

Syntax is better viewed as the dynamics of a morphogenetic field on a semantic universe of “content” words. This may take widely different forms, making the acquisition of any language by an aspiring speaker an entirely new experience. The existence of an underlying “universal syntax” might be illusory.

Many stage‐specific embryonic antigens (SSEAs) have been identified as glycoconjugates. These molecules may play diverse roles in the development of the embryo, including regulation of cell growth, recognition, and differentiation. The example of SSEA‐1 is described in detail. This molecule appears to play an essential role in compaction of the early mouse embryo, and may illustrate the general importance of carbohydrate‐carbohydrate interactions in controlling cell surface interactions in development.

The present account aims to contribute to a better characterization of the state and the dynamics of embryological knowledge at the dawn of the molecular revolution in biology. In this study, Albert Dalcq (1893-1973) was chosen as a representative of a generation of embryologists who found themselves at the junction of two very different approaches to the study of life: the first, focusing on global properties of organisms; the second focusing on the characterization of basic molecular constituents. Though clearly belonging (...) to the organismic tradition, Dalcq was already blending his experimental and explanatory practices with biochemical aspects by the 1930s. Principally based on published sources, the present analysis focuses on the conceptual definitions, modifications and interrelations on which Dalcq's explanation of development rested. Among these are variant process concepts such as gradients and fields, which are often thought to have strongly holistic implications. I will argue that Dalcq's version of these concepts was compatible with a more reductionist treatment of embryos than was accepted by most embryologists as late as the 1950s, pointing to some extent toward the recent molecular characterization of gradients by molecular geneticists such as Christiane Nüsslein-Volhard. Moreover, I will show how the embryological research program of Dalcq and his pupil Jean Brachet has been largely instrumental in the development of molecular biology in Belgium. (shrink)

Negative words or integrated negations: Nothingness, the completely Other, Nothing, the Infinite, the Unknowable, the Subconscious all have a certain poetic overtone. But we must be careful of linguistic sleight-of-hand taken for an idea.

Small GTPases in the Rho family act as major nodes with functions beyond cytoskeletal rearrangements shaping the Caenorhabditis elegans embryo during development. These small GTPases are key signal transducers that integrate diverse developmental signals to produce a coordinated response in the cell. In C. elegans, the best studied members of these highly conserved Rho family small GTPases, RHO‐1/RhoA, CED‐10/Rac, and CDC‐42, are crucial in several cellular processes dealing with cytoskeletal reorganization. In this review, we update the functions described for the (...) Rho family small GTPases in spindle orientation and cell division, engulfment, and cellular movements during C. elegans embryogenesis, focusing on the Rho subfamily Rac.Please also see the video abstract here. (shrink)

Although female and male gametes are presumably equivalent in their genetic contribution to embryos, they carry specific information, perhaps reversibly imprinted into the genomes during oogenesis and spermatogenesis, as to their maternal or paternal origin. This information is crucial for embryogenesis and, in the absence of at least one haploid set of chromosomes from each parent, embryos do not develop to term. The paternal genome is probably required for proliferation of extraembryonic tissues and the maternal genome for some stages (...) of embryogeneis. Furthermore, the effects of certain mutations are determined by the paternal or maternal origin of the inheritance. (shrink)

Although several theoretical approaches consider general methods for dealing with shape, recent observations and experimental data show that embryos exhibit marked changes in the properties of the biological material involved in shape development and shape regulation capacity. In vivo experiments have shown that the amphibian embryo gradually develops from a situation in which it is not able to maintain its shape to one in which it can not only maintain its shape but also possesses a maximal tolerance towards deformation together (...) with a maximal shape regulation capacity. So far two especially clear conclusions have emerged: (i) the form of the embryo appears to be determined by cell activities intrinsic to each stage, and (ii) the morphogenetic programme can be executed normally within wide limits notwithstanding dramatic deformations of the embryo during quite a long period. Thus the hypothesis may be advanced that shape and morphogenesis to some extent become independent phenomena during embryonic development. (shrink)

Development of an animal embryo involves the coordination of cell divisions, a variety of inductive interactions and extensive cellular rearrangements. One of the biggest challenges in developmental biology is to explain the relationships between these processes and the mechanisms that regulate them. Teleost embryos provide an ideal subject for the study of these issues. Their optical lucidity combined with modern techniques for the marking and observation of individual living cells allow high resolution investigations of specific morphogenetic movements and the construction (...) of detailed fate maps. In this review we describe the patterns of cell divisions, cellular movements and other morphogenetic events during zebrafish early development and discuss how these events relate to the formation of restricted lineages. (shrink)

In 2012, we published a computational automaton, based on the most comprehensive gene regulatory network (GRN) model yet available (Peter, Faure, and Davidson 2012). This model had been synthesized over the previous years from extensive experimental studies on specification mechanisms in the endomesodermal territories of the sea urchin embryo. The GRN model explicitly indicated the dynamically changing interactions occurring at the cis-regulatory control sequences of almost 50 genes, mostly encoding transcription factors (the proteins that specifically recognize cis-regulatory DNA sequence and (...) cause expression or inactivity of the genes these sequences control). The GRN model encompasses all regulatory genes .. (shrink)

This article pursues overlapping points about ontology, philosophical method, and our kinship with and difference from nonhuman animals. The ontological point is that being is determinately different in different places not because of differences, or even a space, already given in advance, but in virtue of a negative in being that is regional and rooted in place, which Mer-leau-Ponty calls the “hollow.” The methodological point is that we tend to miss this ontological point because we are inclined to what I (...) call transportable thinking, which conceives of things and spatial determinacy itself as being what they are independent of where they are. I argue that we are inclined this way because, in contrast to other animals, we have a weak sense of where we are. We are lost animals. To compensate for lostness, we abstract ourselves from place and conceptualize ourselves and things by way of a transportable, Cartesian “view from above.”. (shrink)

Embryonic development results in animals whose body plans exhibit a variety of symmetry types. While significant progress has been made in understanding the molecular events underlying the early specification of the antero‐posterior and dorso‐ventral axes, little information has been available regarding the basis for left‐right (LR) differences in animal morphogenesis. Recently however, important advances have been made in uncovering the molecular mechanisms responsible for LR patterning. A number of genes (including well‐known signaling molecules such as Sonic hedgehog and activin) are (...) asymmetrically expressed in early chick embryos, well before the appearance of morphological asymmetries. One of these, nodal, is asymmetrically expressed in frogs and mice as well, and its expression is altered in mouse mutants exhibiting defects in laterality. In the chick, these genes regulate each other in a sequential cascade, which independently determines the situs of the heart and other organs. (shrink)

Early embryogenesis is marked by a frail Spindle Assembly Checkpoint (SAC). The time of SAC acquisition varies depending on the species, cell size or a yet to be uncovered developmental timer. This means that for a specific number of divisions, biorientation of sister chromatids occurs unsupervised. When error‐prone segregation is an issue, an aneuploidy‐selective apoptosis system can come into play to eliminate chromosomally unbalanced cells resulting in healthy newborns. However, aneuploidy content can be too great to overcome, endangering viability.SAC (...) generates a diffusible signal to lengthen time spent in mitosis if needed, ensuring correct chromosome segregation, a fundamental factor in the generation of euploid cells. Thus, it remains puzzling what benefit could come from delaying SAC acquisition till later in the development. In this review, we describe what is known on SAC acquisition in distinct species and highlight pending research as well as potential applications for such knowledge. (shrink)

The identification of molecules controlling embryonic patterning and their functional analysis has revolutionized the fields of Developmental and Cell Biology. The use of new sequence information and modern bioinformatics tools has enriched the list of proteins that could potentially play a role in regulating cell behavior and function during early development. The recent application of efficient methods for gene knockout in zebrafish has accelerated the functional analysis of many proteins, some of which have been overlooked due to their small size. (...) Two recent publications report on the identification of one such protein and its role in zebrafish embryogenesis. The protein, currently designated Apela, was shown to act as a secreted protein whose absence adversely affected various early developmental processes. Additional signaling proteins that have been identified in one of the studies are likely to open the way to unraveling hitherto unknown developmental pathways and have the potential to provide a more comprehensive understanding of known developmental processes. (shrink)

Freeman's pioneering work -- and neurodynamics in general -- has largely ignored specification of an anatomical framework within which features of coherent objects are represented, associated, deleted, and manipulated in computations. Recent theoretical work suggests such a framework can emerge during embryogenesis by selection of neuron ensembles and synaptic connections that maximize the magnitude of synchrony while approaching ultra-small-world connectivity. The emergent structures correspond to those of both columnar and non-columnar cortex. With initial connections thus organized, spatio-temporal information in (...) sensory inputs can generate systematic and specific patterns of synchronous oscillation, with consequent synaptic storage. The theoretical assemblies of connections resemble experimentally observed 'lego sets', while facilitation and interference among synchronous patterns, particularly when executed by fast synapses under metabolic entanglement, imply powerful parallel computation. (shrink)

Historically embryogenesis has been among the most philosophically intriguing phenomena. In this paper I focus on one aspect of biological development that was particularly perplexing to the ancients: self-organisation. For many ancients, the fact that an organism determines the important features of its own development required a special model for understanding how this was possible. This was especially true for Aristotle, Alexander, and Simplicius, who all looked to contemporary technology to supply that model. However, they did not all agree (...) on what kind of device should be used. In this paper I explore the way these ancients made use of technology as a model for the developing embryo. I argue that their different choices of device reveal fundamental differences in the way each thinker understood the nature of biological development itself. In the final section of the paper I challenge the traditional view (dating back to Alexander's interpretation of Aristotle) that the use of automata in GA can simply be read off from their use in the de motu. (shrink)

During embryogenesis, cell division must be spatially and temporally regulated with respect to other developmental processes. Leech embryos undergo a series of unequal and asynchronous cleavages to produce individually recognizable cells whose lineages, developmental fates and cell cycle properties have been characterized. Thus, leech embryos provide an opportunity to examine the regulation of cell division at the level of individual well‐characterized cells within a community of different types of cells. Isolation of leech homologues of some of the highly conserved (...) regulators of the cell division cycle, and characterization of their patterns of maternal and zygotic expression, indicate that the cell divisions of early leech embryos are regulated by cell type‐specific mechanisms. These studies with leech embryos contribute to the emerging appreciation of the diverse mechanisms by which animals regulate cell division during early development. (shrink)

Embryogenesis requires the precise movement and reorganization of many cell and tissue types. Presumably, cell surface receptors allow cells to interact selectively with adjacent cells and with the extracellular environment, as well as initiate differentiative events by transducing appropriate signals across the plasma membrane. One cell surface component that serves as a receptor during a variety of cellular interactions is β1,4‐galactosyltransferase. Cell surface galactosyltransferase participates in diverse cellular interactions by binding its specific glycoconjugate substrate on adjacent cell surfaces or (...) in the extracellular matrix. Biochemical, immunological, and molecular probes are being used to better define cell surface galactosyl‐transferase functional in cellular interactions during fertilization, intercellular adhesion, cell migration, and growth control. (shrink)

During embryogenesis, the basic axon scaffold of the nervous system is formed by special axons that pioneer pathways between groups of cells. To find their way, the pioneer growth cones detect specific cues in their extracellular environment. One of these guidance cues is netrin. Observations and experimental manipulations in vertebrates and nematodes have shown that netrin is a bifunctional guidance cue that can simultaneously attract and repel axons. During the formation of this basic axon scaffold in Caenorhabditis elegans, the (...) netrin UNC‐6 is expressed by neuroglia and pioneer neurons, providing hierarchical guidance cues throughout the animal. Each cue has a characteristic role depending on the cell type, its position and the developmental stage. These roles include activities as global, decussation and labeled‐pathway cues. This hierarchical model of UNC‐6 netrin‐mediated guidance suggests a method by which guidance cues can direct formation of basic axon scaffolds in developing nervous systems. (shrink)

Although bone development during embryogenesis and bone repair after injury have a number of features which appear similar, they are distinctly different processes which involve separate controlling elements and cuing parameters. Repair of bone is influenced by bioactive factors which reside in bone itself; some of these factors are not present when embryonic mesenchymal cells first differentiate. For example, a bone protein which induces the conversion of mesenchymal cells into cartilage cells is not present in the embryo at the (...) site where cartilage first differentiates into the anlagen for future bone. Ultimately, the sequence of cellular and molecular events which controls the success of bone repair is dependent on the prior embryologic and developmental packaging of bioactive factors into bone and the release of these factors at a bone break site. The success of the reparative events depends not only upon the release of these bone‐derived factors but also on systemic factors and the identity and numbers of responding cells at the repair site. (shrink)

The process of embryogenesis poses numerous philosophical puzzles. Conceptual difficulties encountered while attempting to clarify the ontological and moral status of the fertilized ovum, for example, are compounded in the minds of some philosophers by the possible occurrence of monozygotic twinning during the earliest stages of embryological development. In light of certain conceptual complexities engendered by this possibility, G.E.M. Anscombe, for example, has come to believe that the pivotal metaphysical query in need of an adequate response is the following: (...) Is the human zygote a single human? The answer to this question is of interest to Anscombe primarily for the role it would play in solving the following puzzle: Suppose that zygote A divides into twins B and B1, such that neither B nor B1 is identical with its twin or with A. It then seems clear that either A, prior to its division, was somehow already B and B1; or A was a single human out of which another human grew ; or A, which was a single human, became two humans, much like an amoeba becomes two amoebae; or A is a "whole human substantial entity". (shrink)

The discovery of mouse embryonic stem cells in 1981 transformed research in mammalian developmental biology and functional genomics. The subsequent generation of human pluripotent stem cells (PSCs) and the development of molecular reprogramming have opened unheralded avenues for drug discovery and cell replacement therapy. Here, I review the history of PSCs from the perspective that long‐term self‐renewal is a product of the in vitro signaling environment, rather than an intrinsic feature of embryos. I discuss the relationship between pluripotent states captured (...) in vitro to stages of epiblast in the embryo and suggest key considerations for evaluation of PSCs. A remaining fundamental challenge is to determine whether naïve pluripotency can be propagated from the broad range of mammals by exploiting common principles in gene regulatory architecture. (shrink)

Embryogenesis involves biochemical patterning as well as mechanical morphogenetic movements, both regulated by the expression of the regulatory genes of development. The reciprocal interplay of morphogenetic movements with developmental gene expression is becoming an increasingly intense subject of investigation. The molecular processes through which differentiation patterning closely regulates the development of morphogenetic movements are today becoming well understood. Conversely, experimental evidence recently revealed the involvement of mechanical cues due to morphogenetic movements in activating mechano-transduction pathways that control both the (...) differentiation and the active morphogenesis of fundamental events in embryonic tissue development. Here I will first focus on the central role the shape of biological structures of the molecular and mesoscopic cell scales plays in mechano-transduction. Then, after a short description of the genetic regulation of the Drosophila embryo mesoderm invagination at gastrulation—one of the best-understood morphogenetic movement of embryogenesis—I will detail the processes of differentiation and of active morphogenesis of Drosophila embryo gastrulation, which require mechano-transduction. Finally, I will explore the putative consequences in evolution of these mechano-transduction events. I speculate that the first ancient multicellular organisms might have emerged from primary morphological and differentiation patterns induced by primitive mechano-sensation effects allowed by mechano-transduction in response to their physical environment, such as touch by gravity or water flows, which might have acted as primitive motor–sensorial systems, thus conditioning the emergence of our primary animal ancestors. (shrink)

All epistemic agents physically consist of parts that must somehow comprise an integrated cognitive self. Biological individuals consist of subunits (organs, cells, molecular networks) that are themselves complex and competent in their own context. How do coherent biological Individuals result from the activity of smaller sub-agents? To understand the evolution and function of metazoan bodies and minds, it is essential to conceptually explore the origin of multicellularity and the scaling of the basal cognition of individual cells into a coherent larger (...) organism. In this paper I synthesize ideas in cognitive science, evolutionary biology, and developmental physiology toward a hypothesis about the origin of Individuality: “Scale-Free Cognition”. I propose a fundamental definition of an Individual based on the ability to pursue goals at an appropriate level of scale and organization, and suggest a formalism for defining and comparing the cognitive capacities of highly diverse types of agents. Any Self is demarcated by a computational surface – the spatio-temporal boundary of events that it can measure, model, and try to affect. This surface sets a functional boundary - a cognitive “light cone” which defines the scale and limits of its cognition. I hypothesize that higher-level goal-directed activity and agency, resulting in larger cognitive boundaries, evolve from the primal homeostatic drive of living things to reduce stress – the difference between current conditions and life-optimal conditions. The mechanisms of developmental bioelectricity - the ability of all cells to form electrical networks that process information - suggests a plausible set of gradual evolutionary steps that naturally lead from physiological homeostasis in single cells to memory, prediction, and ultimately complex cognitive agents, via scale-up of the drive of infotaxis. Recent data on the molecular mechanisms of pre-neural bioelectricity suggest a model of how increasingly sophisticated cognitive functions emerge smoothly from cell-cell communication used to guide embryogenesis and regeneration. This set of hypotheses provides a novel perspective on numerous phenomena, such as cancer, and makes several unique, testable predictions for interdisciplinary research that have implications not only for evolutionary developmental biology but also for biomedicine and perhaps artificial intelligence and exobiology. (shrink)

RNA localization is a powerful strategy used by cells to localize proteins to subcellular domains and to control protein synthesis regionally. In germ cells, RNA targeting has profound implications for development, setting up polarities in genetic information that drive cell fate during embryogenesis. The frog oocyte offers a useful system for studying the mechanism of RNA localization. Here, we discuss critically the process of RNA localization during frog oogenesis. Three major pathways have been identified that are temporally and spatially (...) separated in oogenesis. Each pathway uses a different mechanism to effect RNA localization. In some cases, localization elements within the 3' untranslated region have been identified and have provided unique insights into the localization process. This important field is still in its infancy, however, and much remains to be learned. BioEssays 21:546–557, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Early development in many animals is programmed by maternally inherited messenger RNAs. Many of these mRNAs are translationally dormant in immature oocytes, but are recruited onto polysomes during meiotic maturation, fertilization, or early embryogenesis. In contrast, other mRNAs that are translated in oocytes are released from polysomes during these later stages of development. Recent studies have begun to define the cis and trans elements that regulate both translational repression and translational induction of maternal mRNA. The inhibition of translation of (...) some mRNAs during early development is controlled by discrete sequences residing in the 3′ and 5′ untranslated regions, respectively. The translation of other RNAs is due to polyadenylation which, at least in oocytes of the frog Xenopus laevis, is regulated by a U‐rich cytoplasmic polyadenylation element (CPE). Although similar, the CPE sequences of various mRNAs are sufficiently different to be bound by different proteins. Two of these proteins and their interactions are described here. (shrink)

Significant progress in the molecular investigation of endogenous bioelectric signals during pattern formation in growing tissues has been enabled by recently developed techniques. Ion flows and voltage gradients produced by ion channels and pumps are key regulators of cell proliferation, migration, and differentiation. Now, instructive roles for bioelectrical gradients in embryogenesis, regeneration, and neoplasm are being revealed through the use of fluorescent voltage reporters and functional experiments using well‐characterized channel mutants. Transmembrane voltage gradients (Vmem) determine anatomical polarity and function (...) as master regulators during appendage regeneration and embryonic left‐right patterning. A state‐of‐the‐art recent study reveals that they can also serve as prepatterns for gene expression domains during craniofacial patterning. Continued development of novel tools and better ways to think about physical controls of cell‐cell interactions will lead to mastery of the morphogenetic information stored in physiological networks. This will enable fundamental advances in basic understanding of growth and form, as well as transformative biomedical applications in regenerative medicine. (shrink)

One of the most fundamental features of the body plan of arthropods is its segmental design. There is considerable variation in segment number among arthropod groups (about 20‐fold); yet, paradoxically, the vast majority of arthropod species have a fixed number of segments, thus providing no variation in this character for natural selection to act upon. However, the 1000‐species‐strong centipede order Geophilomorpha provides an exception to the general rule of intraspecific invariance in segment number. Members of this group, and especially our (...) favourite animal Strigamia maritima, may thus help us to understand the evolution of segment number in arthropods. Evolution must act by modifying the formation of segments during embryogenesis. So, how this developmental process operates, in a variable‐segment‐number species, is of considerable interest. Strigamia maritima turns out to be a tractable system both at the ecological level of investigating differences in mean segment number between populations and at the molecular level of studying the expression patterns of developmental genes. Here we report the current state of play in our work on this fascinating animal, including our recent finding of a double‐segment periodicity in the expression of two Strigamia segmentation genes, and its possible implications for our understanding of arthropod segmentation mechanisms in general. BioEssays 27:653–660, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The establishment of a functional vascular system requires multiple complex steps throughout embryogenesis, from endothelial cell (EC) specification to vascular patterning into venous and arterial hierarchies. Following the initial assembly of ECs into a network of cord‐like structures, vascular expansion and remodeling occur rapidly through morphogenetic events including vessel sprouting, fusion, and pruning. In addition, vascular morphogenesis encompasses the process of lumen formation, critical for the transformation of cords into perfusable vascular tubes. Studies in mouse, zebrafish, frog, and human (...) endothelial cells have begun to outline the cellular and molecular requirements underlying lumen formation. Although the lumen can be generated through diverse mechanisms, the coordinated participation of multiple conserved molecules including transcription factors, small GTPases, and adhesion and polarity proteins remains a fundamental principle, leading us closer to a more thorough understanding of this complex event. (shrink)

Abstractftz is one of the ‘pair rule’ segmentation genes of Drosophila melanogaster, and is an important component of the segmentation process in the fruit fly. We discuss the transcriptional mechanism which causes ftz to be expressed in a seven stripe pattern during embryogenesis.

The recent discovery of a phenomenon of craniofacial growth, called craniofacial contraction, throws a new light on the process of hominization. The main interest of this discovery lies in a growth principle combining the different craniofacial units, that is to say, the neurocranium, the chondrocranium and the splanchnocranium. Until recent years, these different parts were considered as neighbouring element without any morphogenic or morphodynamic connection. But now, we know that the morphogenesis of the base of the skull governs that of (...) the face. This basicranial morphogenesis is the occipital flexion. It generates morphogenic correlations with the face since embryogenesis. The ontogenic pathway of this phenomenon is the craniofacial contraction. It concerns embryonic dynamics connected with the spatial development of the embryonic neural system, the neural tube. These morphodynamics are common to each primate species, but they are differenciated by the amplitude of the embryonic contraction. We ask ourself the question: is hominization of the neurocephalic embryogenesis, that is the craniofacial contraction, plausible over a very long period, with gradual and chaotic evolutionary pathways, or, on the contrary, is the complexity of such an embryonic phenomenon, a limiting factor generating determined and predictible ontogenic thresholds? The study of extant and fossil primate skulls demonstrates that species are organized around 6 levels of embryonic contraction, which, starting from 60 millions years, evolve from the less to the most contracted skull. Among each ontogenic level, living and fossil species develop from the same embryonic system but between both levels, the embryos suddenly are reorganized. Therefore, I have defined an evolutive ontogenic unity, that is the fundamental ontogenesia. The cephalic pole has a fundamental ontogenesis, meaning that, beyond the diversities, we can see the same contraction in many living and extinct species. The ontogenic diversities are the result of the microevolution and are not predictible. In such a perspective, the ontogenic morphodynamics evolve with chaotic trajectories. But, between two embryonic levels, or two fundamental ontogeneses, evolutionary modalities are different. Eventually, from 60 millions years to XXth century, we observe the same phenomenon than during human ontogenesis; hominization of the cephalic pole is a craniofacial contraction. The evolutive pathway is stable, whatever the number of thresholds, the cranial shape changes but the ontogenic trajectory is preserved. This is a macroevolution because the embryonic system is reorganized. The logics of the phenomenon are an increasing dynamization, the human ontogenesis is the more unstable and the longer morphodynamics to stabilize the craniofacial contraction. To conclude, hominization is an iteration of an ontogenic process when embryos reach successive dynamic thresholds. The attractors are neither static, periodic, nor chaotic because the successive ontogenic trajectories are themselves in a stable evolutive trajectory, and the results with increasing contraction, complexified neocortical tissues and cephalocaudal reorganization are predictible. During hominization, irreversibility and innovations do not emerge with chaotic determinism, but with harmonic determinism in association with the correlations established between the embryonic tissues. When the system is destabilized, the embryonic systems do not forget the previous ontogenic pattern, on the contrary, they develop the pattern with new dynamical conditions. This sort of phenomenon is not described in the sciences of complexity. In the present case, we are in front of many millions years and the necessity to propose new concepts such as a new familly of attractors, namely the harmonic attractors. (shrink)

We have discovered that a single sperm protein, phospholipase C‐zeta (PLCζ), can stimulate intracellular Ca2+ signalling in the unfertilized oocyte (‘egg’) culminating in the initiation of embryonic development. Upon fertilization by a spermatozoon, the earliest observed signalling event in the dormant egg is a large, transient increase in free Ca2+ concentration. The fertilized egg responds to the intracellular Ca2+ rise by completing meiosis. In mammalian eggs, the Ca2+ signal is delivered as a train of long‐lasting cytoplasmic Ca2+ oscillations that begin (...) soon after gamete fusion and persist beyond the completion of meiosis. Sperm PLCζ effects Ca2+ release from egg intracellular stores by hydrolyzing the membrane lipid PIP2 and consequent stimulation of the inositol 1,4,5‐trisphosphate (InsP3) receptor Ca2+‐signalling pathway, leading to egg activation and early embryogenesis. Recent advances have refined our understanding of how PLCζ induces Ca2+ oscillations in the egg and also suggest its potential dysfunction as a cause of male infertility. (shrink)

Morphogenesis is a general concept in biology including all the processes which generate tissue shapes and cellular organizations in a living organism. Many hybrid formalizations have been proposed for modelling morphogenesis in embryonic or adult animals, like gastrulation. We propose first to study the ventral furrow invagination as the initial step of gastrulation, early stage of embryogenesis. We focus on the study of the connection between the apical constriction of the ventral cells and the initiation of the invagination. For (...) that, we have created a 3D biomechanical model of the embryo of the Drosophila melanogaster based on the finite element method. Each cell is modelled by an elastic hexahedron contour and is firmly attached to its neighbouring cells. A uniform initial distribution of elastic and contractile forces is applied to cells along the model. Numerical simulations show that invagination starts at ventral curved extremities of the embryo and then propagates to the ventral medial layer. Then, this observation already made in some experiments can be attributed uniquely to the specific shape of the embryo and we provide mechanical evidence to support it. Results of the simulations of the “pill-shaped” geometry of the Drosophila melanogaster embryo are compared with those of a spherical geometry corresponding to the Xenopus lævis embryo. Eventually, we propose to study the influence of cell proliferation on the end of the process of invagination represented by the closure of the ventral furrow. (shrink)

Vascular Endothelial Growth Factor (VEGF) is the most potent and ubiquitous vascular growth factor known to date. Yet, prior to its description as a secreted mitogen for endothelial cells, it was identified as a vascular permeability factor. These seemingly disparate avenues of discovery highlight VEGF's ability to control many distinct aspects of endothelial cell behaviour, including proliferation, migration, specialisation and survival. The versatility of VEGF as a patterning molecule is likely linked to its association with various signalling receptor complexes, but (...) also its expression in several isoforms with a differential affinity for heparan sulfate proteoglycans in the extracellular matrix. In contrast to the absolute requirement for all known VEGF receptors, the presence of only a single VEGF isoform is sufficient for vascular development. However, the isoforms serve as exquisite tools for the fine patterning of growing vessel networks during embryogenesis and in postnatal life. BioEssays 25:1052–1060, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Early in his career Thomas Hunt Morgan was interested in embryology and dedicated his research to studying organisms that could regenerate. Widely regarded as a regeneration expert, Morgan was invited to deliver a series of lectures on the topic that he developed into a book, Regeneration. In addition to presenting experimental work that he had conducted and supervised, Morgan also synthesized and critiqued a great deal of work by his peers and predecessors. This essay probes into the history of regeneration (...) studies by looking in depth at Regeneration and evaluating Morgan’s contribution. Although famous for his work with fruit fly genetics, studying Regeneration illuminates Morgan’s earlier scientific approach which emphasized the importance of studying a diversity of organisms. Surveying a broad range of regenerative phenomena allowed Morgan to institute a standard scientific terminology that continues to inform regeneration studies today. Most importantly, Morgan argued that regeneration was a fundamental aspect of the growth process and therefore should be accounted for within developmental theory. Establishing important similarities between regeneration and development allowed Morgan to make the case that regeneration could act as a model of development. The nature of the relationship between embryogenesis and regeneration remains an active area of research. (shrink)

The relationship of embryonal carcinoma (EC) cells, the stem cells of germ cell‐ or embryo‐derived teratocarcinoma tumors, to early embryonic cells came under intense scrutiny in the early 1970s when mouse chimeras were produced between EC cells and embryos. These chimeras raised tantalizing possibilities and high hopes for different areas of research. The normalization of EC cells by the embryo lent validity to their use as in vitro models for embryogenesis and indicated that they might reveal information about the (...) relationship between malignancy and differentiation. Chimeras also showed the way for the potential introduction of genes, selected in EC cells in vitro, into the germ line of mice. Although EC cells provided material for the elucidation of early embryonic events and stimulated many studies of early molecular differentiation, after years of intense scrutiny, they fell short as the means of genetic manipulation of the germ line, although arguably they pointed the way to the development of embryonic stem (ES) cells that eventually fulfilled this goal. (shrink)

Regeneration capabilities are found in most or all animals. Whether regeneration is part of the development of an animal or a distinct phenomenon independent of development is a debatable question. If we consider regeneration as a process belonging to development, similarly to embryogenesis or metamorphosis, the existence of regenerative capabilities in adults can be seen as an argument in favor of the theory that development continues throughout the life of animals. Here I perform a comparative analysis of regeneration versus (...) “classical” developmental processes in animals in order to determine to what extent these processes are inclusive or distinct. I identify the existence of regeneration-specific processes, i.e., processes that occur during the regeneration, but not the initial development, of a given structure. In addition, I find that seemingly similar processes acting during development and regeneration may have differential molecular and cellular bases. I thus conclude that there are significant differences between regeneration processes in adult animals and developmental processes occurring during earlier phases of the life cycle. The existence of regenerative capabilities in adult animals can therefore not be used as an argument in favor of the idea that development spans the whole life. (shrink)

Recent molecular evidence suggests that the body plans of insects and vertebrates may be dorsoventrally inverted with respect to one another. This poses a major challenge for comparative zoologists, either to explain how this came about or to offer alternative interpretations of the data. Dorsoventral inversion is most easily explained if the mouth of deuterostome metazoans (which would include vertebrates) is truly a secondary structure unrelated to the protostome mouth, located opposite to the latter on the dorsal surface of the (...) body. Two possibilities are (1) that the definitive deuterostome mouth has replaced a preexisting protostome‐type mouth, or (2) that ancestral deuterostomes lacked a protostome‐type mouth altogether, and formed a secondary dorsal mouth entirely de novo. Our current understanding of invertebrate embryogenesis and larval morphology provides at least as much support, if not more, for (2) as for (1). By implication, even if ancestral protostomes and deuterostomes shared common anteroposterior and dorsoventral patterning systems, they may still have differed significantly with respect to other aspects of body organization and been otherwise very dissimilar organisms. (shrink)

At the end of the nineteenth century, approaches from experimental physiology made inroads into embryological research. A new generation of embryologists felt urged to study the mechanisms of organ formation. This new program, most prominently defended by Wilhelm Roux, was called Entwicklungsmechanik. Named variously as “causal embryology”, “physiological embryology” or “developmental mechanics”, it catalyzed the movement of embryology from a descriptive science to one exploring causal mechanisms. This article examines the specific scientific and epistemological meaning of the mechanistic approaches of (...) embryological development by focusing on Wilhelm His’ histogenetic work. Roux was neither the first, nor the only one to argue for an experimental exploration of causes in embryology. At the time of Roux, physiological explanations of the genesis of the anatomical forms were developing in parallel, not only in German-speaking countries, but in France, Switzerland and English-speaking countries as well. The experimental approach and the cellular descriptions of embryogenesis were already omni-present when Roux proposed his Entwicklungsmechanik. However, these approaches remained disjointed. It appears that it was Wilhelm His who first succeeded in combining the question of the causal factors determining epigenesis, which was closely connected with experimentation on, and cellular descriptions of, development, in a coherent and concrete synthesis, making him one of the true initiators of the developmental mechanics. (shrink)