This history of a statement attributed to the developmental biologist Lewis Wolpert exemplifies the making and uses of quotations in recent science. Wolpert's dictum, ‘It is not birth, marriage or death, but gastrulation which is truly the most important time in your life’, was produced in a series of international shifts of medium and scale. It originated in his vivid declaration in conversation with a non-specialist at a workshop dinner, gained its canonical form in a colleague's monograph, and was (...) amplified as a quotation on a poster derived from an undergraduate project. Although it drew on Wolpert's authority and he accepted his authorship, it thus represents a collective sifting of earlier claims for the significance of prenatal existence through the values of 1980s developmental biology. Juxtaposing a technical term with major life events has let teachers engage students, and researchers entice journalists, while sharing an in-joke that came to mark community identity. Serious applications include arguing for an extension of the fourteen-day limit on human-embryo research. On this evidence, quotations have been kept busy addressing every audience of specialized knowledge. (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)

Understanding the events that led to the emergence of the bilaterians is a daunting task, impaired by the huge evolutionary gap separating us from the pre‐Cambrian. During gastrulation, the expression of the transcription factor Brachyury is remarkably well conserved around the blastopore of bilaterians and cnidarians. Only the bilaterian Brachyury proteins, however, share a distinctive N‐terminal sequence not found in outgroups such as cnidarians, sponges or placozoans. We now know that, in vertebrates, this N‐terminal domain confers specific transcriptional activity, (...) by recruiting Smad1, the first identified co‐factor for Brachyury. Smad1 is an effector of the BMP pathway, and has been isolated in bilaterians and cnidarians. Here, I propose that the protein–protein interaction between Brachyury and Smad1 represents an evolutionary novelty of the Urbilateria. The gain of the N‐terminal domain might have been selected to spatially modulate the activity of Brachyury, thereby facilitating the establishment of bilateral symmetry during gastrulation movements. BioEssays 28: 413–420, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Der Abschluß der Gastrulation, der gleichzeitig auch den Anfang der Neurulation bedeutet, ist die zeitliche Grenze, die Beginn eines menschlichen Individuums markiert. Oft wird behauptet, daß jegliche natürliche Veränderung stetig ist. Wie ist es dann aber möglich, eine zeitliche Grenze auszuzeichnen, an der ein menschliches Lebewesen zu existieren beginnt? Man beachte, was geschieht, wenn wir vom Thema zeitlicher Unstetigkeit zum räumlichen übergehen. Lebewesen haben räumliche Grenzen (wie sie durch ihre Haut geformt wird). Die letzteren sind genuine Diskontinuitäten, auch angesichts (...) der Kontinuität der Materie in der physikalischen Welt. Und ebenso müssen wir schließen: Das Leben menschlicher Lebewesen hat zeitliche Grenzen - seinen Beginn und sein Ende - die auch angesichts der Kontinuität physikalischer, chemischer und biologischer Prozesse, in die sie involviert sind, echte Diskontinuitäten sind. (shrink)

Gastrulation is the process of early development that reorganizes cells into the three fundamental tissue types of ectoderm, mesoderm, and endoderm. It is a coordinated series of morphogenetic and molecular changes that exemplify many developmental phenomena. In this review, we explore one of the classic developmental systems, the sea urchin embryo, where investigators from different backgrounds have converged on a common interest to study the origin, morphogenesis, and developmental regulation of the endoderm. The sea urchin embryo is remarkably plastic (...) in its developmental potential, and the endoderm is especially instructive for its morphological and molecular responsiveness to inductive cell interactions. We start by examining and integrating the several models for the morphogenetic mechanisms of invagination and tissue elongation, the basic processes of endoderm morphogenesis in this embryo. We next critique the proposed mechanisms of inductive gene regulation in the endoderm that exemplifies a concept of modular transcriptional regulation. Finally, we end with an examination of the current molecular models to explain cell fate determination of the endoderm. Recent progress at the molecular level should soon allow us to explain the seminal experimental observations made in this embryo over a hundred years ago. BioEssays 21:459–471, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Der Abschluß der Gastrulation, der gleichzeitig auch den Anfang der Neurulation bedeutet, ist die zeitliche Grenze, die Beginn eines menschlichen Individuums markiert. Oft wird behauptet, daß jegliche natürliche Veränderung stetig ist. Wie ist es dann aber möglich, eine zeitliche Grenze auszuzeichnen, an der ein menschliches Lebewesen zu existieren beginnt? Man beachte, was geschieht, wenn wir vom Thema zeitlicher Unstetigkeit zum räumlichen übergehen. Lebewesen haben räumliche Grenzen (wie sie durch ihre Haut geformt wird). Die letzteren sind genuine Diskontinuitäten, auch angesichts (...) der Kontinuität der Materie in der physikalischen Welt. Und ebenso müssen wir schließen: Das Leben menschlicher Lebewesen hat zeitliche Grenzen - seinen Beginn und sein Ende - die auch angesichts der Kontinuität physikalischer, chemischer und biologischer Prozesse, in die sie involviert sind, echte Diskontinuitäten sind. (shrink)

Der Abschluß der Gastrulation, der gleichzeitig auch den Anfang der Neurulation bedeutet, ist die zeitliche Grenze, die Beginn eines menschlichen Individuums markiert. Oft wird behauptet, daß jegliche natürliche Veränderung stetig ist. Wie ist es dann aber möglich, eine zeitliche Grenze auszuzeichnen, an der ein menschliches Lebewesen zu existieren beginnt? Man beachte, was geschieht, wenn wir vom Thema zeitlicher Unstetigkeit zum räumlichen übergehen. Lebewesen haben räumliche Grenzen (wie sie durch ihre Haut geformt wird). Die letzteren sind genuine Diskontinuitäten, auch angesichts (...) der Kontinuität der Materie in der physikalischen Welt. Und ebenso müssen wir schließen: Das Leben menschlicher Lebewesen hat zeitliche Grenzen - seinen Beginn und sein Ende - die auch angesichts der Kontinuität physikalischer, chemischer und biologischer Prozesse, in die sie involviert sind, echte Diskontinuitäten sind. (shrink)

When did we begin to exist? Barry Smith and Berit Brogaard argue that a new human organism comes into existence neither earlier nor later than the moment of gastrulation: 16 days after conception. Several critics have responded that the onset of the organism must happen earlier; closer to conception. This article makes a radically different claim: if we accept Smith and Brogaard’s ontological commitments, then human organisms start, on average, roughly nine months after conception. The main point of contention (...) is whether the fetus is or is not part of the maternal organism. Smith and Brogaard argue that it is not; I demonstrate that it is. This claim in combination with Smith and Brogaard’s own criteria commits to the view that human organisms begin, precisely, at birth. (shrink)

The question of when human life begins is critical in debates related to life issues. While there are a variety of proposals as to how an organism should be defined, many biologists and ethicists, particularly Catholics, have approached this issue by arguing that fertilization defines the beginning of a new organism. Examining the processes of fission and fusion, which take place before gastrulation, provides strong evidence for when human life beings and therefore how it should be defined. Among the (...) four dominant theories, regulative fission and fusion are the best explanations in terms of being the most consistent with the biological data. This explanation of twinning provides compelling evidence that fertilization is not a necessary condition for human generation, although it may be a sufficient condition. While fertilization generates the vast majority of human beings, additional human beings may rarely be generated during fission events. (shrink)

Morphogenesis is one of the fundamental processes of developing life. Gastrulation, especially, marks a period of major translocations and bustling rearrangements of cells that give rise to the three germ layers. It was also one of the earliest fields in biology where cell movement and behaviour in living specimens were investigated. This article examines scientific attempts to understand gastrulation from the point of view of cells in motion. It argues that the study of morphogenesis in the twentieth century (...) faced a major dilemma, both epistemological and pictorial: representing form and understanding movement are mutually exclusive, as are understanding form and representing movement. The article follows various ways of modelling, imaging, and simulating gastrular processes, from the early twentieth century to present-day systems biology. The first section examines the tactile modelling of shape changes, the second cell cinematography, mainly the pioneering work of the German embryologists Friedrich Kopsch and Ernst Ludwig Gräper in the 1920s but also a series of classic, yet not widely known, studies of the 1960s. The third section deals with the changes that computer simulation and live-cell imaging introduced to the modelling of shape change and the study of cell movement at the turn of the twenty-first century. Although live-cell imaging promises to experiment upon and represent the living body simultaneously, I argue that the new visuals are an obstacle rather than a solution to the puzzle of understanding cell motion. (shrink)

When does a human being begin to exist? Barry Smith and Berit Brogaard have argued that it is possible, through a combination of biological fact and philosophical analysis, to provide a definitive answer to this question. In their view, a human individual begins to exist at gastrulation, i. e. at about sixteen days after fertilization. In this paper we argue that even granting Smith and Brogaard's ontological commitments and biological assumptions, the existence of a human being can be shown (...) to begin much earlier, viz., with fertilization. Their interpretative claim that a zygote divides immediately into two substances and therefore ceases to exist is highly implausible by their own standards, and their factual claim that there is no communication between the blastomeres has to be abandoned in light of recent embryological research. (shrink)

It seems that at conception something is formed which, due to its genetic make-up, has the potentiality to develop into a full-blown human being. Many believe that in virtue of this potentiality, this organism, the human zygote or early embryo, has an intrinsic value which makes it wrong to use or produce it merely as a means to some end, e.g., some scientific end such as to produce embryonic stem cells. Against this it is here argued, first, that it does (...) not follow from the fact that something has a potential to become a human being that it already is a human being. In fact, a human being begins to exist no earlier than a couple of weeks after conception, at the stage known as gastrulation. Thus, even granted the questionable assumption that something has intrinsic value in virtue of being a human being, the zygote will not have intrinsic value. Secondly, the value an embryo has in virtue of its potentiality to become a full-blown human being can only be instrumental, a value as a means. But Of course it cannot be wrong to treat that which has merely instrumental value as a mere means or instrument to some end. (shrink)

Cells can transit between a range of stable epithelial and mesenchymal states and this has allowed the evolution of complex body forms. Epithelial to mesenchymal transition (EMT) and its reverse, mesenchymal to epithelial transition (MET), occur sequentially in development and organogenesis. EMT often accompanies transitions between stem‐like cells and their more differentiated progeny, as occurs at gastrulation, although the relevance of this had not been clarified. New findings from the cancer and cell reprogramming fields suggest that EMT and MET (...) can act as essential portals to stem cell character. Here, we review these findings in the broader context of EMT and MET with emphasis on stem cell biology. Using the heart as an example, we also explore the potential role of EMT/MET in organ regeneration. Understanding EMT and MET at a network level will give us new tools to probe stem cell character and enhance tissue repair. (shrink)

In the last few years, an understanding has emerged of the developmental mechanism for the consistent internal left–right structure, termed situs, that characterises vertebrate anatomy. This involves largely vertebrate‐conserved (i.e. ‘phylotypic’) gene expression cascades that encode ‘leftness’ and ‘rightness’ in appropriate tissues either side of the embryo's midline soon after gastrulation. Recent evidence indicates that the initial, directional symmetry breaking that initiates these cascades utilises mechanisms that are conserved or at least closely related in different vertebrate types. I describe (...) a scenario whereby the capacity for directional modification of an otherwise bilateral body plan can be viewed as an adaptive innovation rather closely connected with vertebrate origins, enabling optimal ‘design’ for very active lifestyles. But an alternative scenario, while retaining the view that situs and indeed other vertebrate functional lateralisations are deeply adaptive, proposes that they originated in the co‐optation of left–right developmental information inherited from a very early stage in metazoan diversification. It is proposed that a remote chordate ancestor lost its original or ‘ur‐bilaterian’ symmetry to pass through an altogether non‐symmetrical stage, and that the vertebrate dorsoventral midline plane is not descended from that original one. I review the considerable evidence in favour of this scenario, and discuss its wider implications for directional asymmetries across the Metazoa. BioEssays 26:413–421, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Mouse embryonic stem cell lines offer an attractive route for introducing rare genetic alternations into the gene pool since the cells can be pre‐screened in culture and the mutations then transmitted into the germline through chimera production. Two applications of this technique seem ideally suited for a genetic analysis of development are enhancer and gene trap screens for loci expressed during gastrulation and production of targeted mutations using homologous recombination. These approaches should greatly increase the number of mouse developmental (...) mutants available and help to elucidate the genetic hierarchy controlling embryogenesis. (shrink)

Formation of a multicellular organism is a complex process involving differentiation and morphogenesis. During early vertebrate development, the radial symmetric organization of the egg is transferred into a bilateral symmetric organism with three distinct body axes: anteroposterior (AP), dorsoventral, and left–right. Due to cellular movements and proliferation, the body elongates along the AP axis. How are these processes coupled? Two recent publications now indicate that cell migration as well as orientated cell divisions contribute to axis elongation. The processes are coupled (...) through the planar cell polarity pathway.1 At the same time, the AP axis is patterned independently of convergent extension. This process, however, is required for cell migration and represents a cue for polarized cell motility during gastrulation. Thus, it is AP polarity that instructs individual cells how to orientate with respect to the embryonic axis and provides positional information for the process of convergent extension.2 BioEssays 26:1272–1275, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The correct positioning of organs during embryonic development requires multiple cues. The Xenopus cement gland is a mucus‐secreting epithelium that is a simple model for organogenesis, allowing detailed analysis of this complex process. The cement gland forms at a conserved anterior position, where embryonic ectoderm and endoderm touch. In all deuterostomes, this region will form the stomodeum (primitive mouth) and, in some aquatic larva, will also form a cement gland. In recent years, a model has been put forward suggesting that (...) an intermediate level of BMP signaling in the ectoderm leads to cement gland formation. We propose an alternative model whereby, during gastrulation, the cement gland (CG) is positioned by the overlap of three domains, corresponding to anterodorsal identity (AD), ventrolateral identity (VL), and ectodermal outer layer identity (EO), defining the equation (AD + VL + EO = CG). Anterodorsal identity requires a contribution by the transcription factor Otx2 while ventrolateral identity requires the BMP4 signaling pathway. These postional cues are integrated to activate cement gland differentiation. This integration appears to require intermediate steps, including expression of pitx genes, and members of the ATF/CREB and Ets transcription factor families. BioEssays 25:717–726, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Evidence from Drosophila and also vertebrates predicts that two different sets of instructions may determine the development of the rostral and caudal parts of the body. This implies different cellular and inductive processes during gastrulation, whose genetic requirements remain to be understood. To date, four genes encoding transcription factors expressed in the presumptive vertebrate head during gastrulation have been studied at the functional level: Lim‐1, Otx‐2, HNF‐3β and goosecoid. We discuss here the potential functions of these genes in (...) the formation of rostral head as compared to posterior head and trunk, and in the light of recent fate map and expression analyses in mouse, chick, Xenopus and zebrafish. These data indicate that Lim‐1, Otx‐2 and HNF‐3β may be involved in the same genetic pathway controlling the formation of the prechordal mesendoderm, which is subsequently required for rostral head development. goosecoid may act in a parallel pathway, possibly in conjunction with other, yet unidentified, factors. (shrink)

The Cambrian explosion is characterized by the sudden outburst of organized animal plans, which occurred circa 530 M years ago. Around that time, many forms of animal life appeared, including several which have since disappeared. There is no general consensus about “why” this happened, and why it had any form of suddenness. However, all organized animal plans share a common feature: they are triploblastic, i.e., composed of 3 layers of tissue, endoderm, ectoderm and mesoderm. I show here that, within simple (...) hypotheses, the formation of the mesoderm has intrinsically a physical exponential dynamics, leading rapidly to triploblastism, and eventually, to animal formation. A novel physico-mathematical framework including epithelium-mesenchyme transition, visco-elastic constitutive equations, and conservation laws, is presented which allows one to describe gastrulation as a self-wetting phenomenon of a soft solid onto itself. This phenomenon couples differentiation and migration during gastrulation, and leads in a closed form to an exponential scaling law for the formation of the mesoderm. Therefore, the Cambrian explosion might have started, actually, by a true visco-elastic “explosion”: the exponential run-away of mesenchymal cells. (shrink)

Six essential genes located near the mouse albino locus have been identified as required during specific periods of development. Amongst these six, each is required either during the preimplantation stages of development, at specific times during gastrulation, within 12 hrs after birth or during juvenile development. These genes were identified as a result of extensive genetic complementation analysis using embryos homozygous for the albino deletions. Although, in principal, the associated developmental abnormalities could result from loss of multiple genes, the (...) deletion phenotype in one case is identical to that induced by chemical mutagenesis. These results indicate that the abnormalities observed in deletion homozygotes may result from single gene loss. The deletions have proven useful not only as genetic tools to localize the position of the genes, but also as molecular entry points to the regions containing these genes. The current methodology being used to isolate candidate genes from the albino region is also reviewed here. (shrink)

First isolated in the fly and now characterised in vertebrates, the Slit proteins have emerged as pivotal components controlling the guidance of axonal growth cones and the directional migration of neuronal precursors. As well as extensive expression during development of the central nervous system (CNS), the Slit proteins exhibit a striking array of expression sites in non-neuronal tissues, including the urogenital system, limb primordia and developing eye. Zebrafish Slit has been shown to mediate mesodermal migration during gastrulation, while Drosophila (...) slit guides the migration of mesodermal cells during myogenesis. This suggests that the actions of these secreted molecules are not simply confined to the sphere of CNS development, but rather act in a more general fashion during development and throughout the lifetime of an organism. This review focuses on the non-neuronal activities of Slit proteins, highlighting a common role for the Slit family in cellular migration. (shrink)

In a recent publication, Wikramanayake and colleagues have implicated the canonical Wnt/β-catenin signaling pathway as a mediator of axial polarity and germ-layer specification in embryos of the cnidarian Nematostella.1 In this anthozoan, β-catenin is localized in nuclei of blastomeres in one region of the 16- to 32-cell embryo whose descendants subsequently form the entoderm of the embryo. They claim that the pattern of nuclear localization is significant for two reasons: (1) when nuclear localization of β-catenin was inhibited, gastrulation does (...) not occur, and (2) when localization of β-catenin took place in all cells of the pregastrula embryo, the number of entodermal cells increases. Since the Wnt/β-catenin signaling pathway also plays a role in establishing axial polarity and specifying endoderm and mesoderm in a number of bilaterians,2-6 Wikramanayake et al. imply that this developmental mechanism is an evolutionary inheritance from a radially symmetrical ancestor. Some of the gaps in the current evidence, which must be filled to evaluate their interpretation, are discussed. BioEssays 26:474–478, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The invariant left–right asymmetry of animal body plans raises fascinating questions in cell, developmental, evolutionary, and neuro‐biology. While intermediate mechanisms (e.g., asymmetric gene expression) have been well‐characterized, very early steps remain elusive. Recent studies suggested a candidate for the origins of asymmetry: rotary movement of extracellular morphogens by cilia during gastrulation. This model is intellectually satisfying, because it bootstraps asymmetry from the intrinsic biochemical chirality of cilia. However, conceptual and practical problems remain with this hypothesis, and the genetic data (...) is consistent with a different mechanism. Based on wide‐ranging data on ion fluxes and motor protein action in a number of species, a model is proposed whereby laterality is generated much earlier, by asymmetric transport of ions, which results in pH/voltage gradients across the midline. These asymmetries are in turn generated by a new candidate for “step 1”: asymmetric localization of electrogenic proteins by cytoplasmic motors. BioEssays 25:1002–1010, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The invariant left–right asymmetry of animal body plans raises fascinating questions in cell, developmental, evolutionary, and neuro‐biology. While intermediate mechanisms (e.g., asymmetric gene expression) have been well‐characterized, very early steps remain elusive. Recent studies suggested a candidate for the origins of asymmetry: rotary movement of extracellular morphogens by cilia during gastrulation. This model is intellectually satisfying, because it bootstraps asymmetry from the intrinsic biochemical chirality of cilia. However, conceptual and practical problems remain with this hypothesis, and the genetic data (...) is consistent with a different mechanism. Based on wide‐ranging data on ion fluxes and motor protein action in a number of species, a model is proposed whereby laterality is generated much earlier, by asymmetric transport of ions, which results in pH/voltage gradients across the midline. These asymmetries are in turn generated by a new candidate for “step 1”: asymmetric localization of electrogenic proteins by cytoplasmic motors. BioEssays 25:1002–1010, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

DNA methylation plays a role in the repression of gene expression in animal cells. In the mouse preimplantation embryo, most genes are unmethylated but a wave of de novo methylation prior to gastrulation generates a bimodal pattern characterized by unmethylated CpG island‐containing housekeeping genes and fully modified tissue‐specific genes. Demethylaton of individual genes then takes place during cell type specific differentiation, and this demodification may be a required step in the process of transcriptional activation. DNA modification is also involved (...) in the maintenance of gene repression on the inactive X chromosome in female somatic cells and the marking of parental alleles at genomically imprinted gene loci. (shrink)

The mesoderm is the region of the embryo that gives rise to muscle, blood and connective tissues; it becomes segregated from the ectoderm and endoderm at gastrulation. Embryological studies have revealed, however, that the potential for certain embryonic cells to become part of the mesoderm is established well before gastrulation, most likely through an extracellular signalling process termed ‘induction’. The recent characterization of mesoderm‐specific mRNAs and proteins now permits an analysis of the very earliest events involved in the (...) specification of the mesoderm at the molecular level. Such experiments should contribute to our understanding of the mechanisms involved in controlling cell differentiation. (shrink)

Spreds form a new protein family with an N‐terminal Enabled/VASP homology 1 domain (EVH1), a central c‐Kit binding domain (KBD) and a C‐terminal Sprouty‐related domain (SPR). They are able to inhibit the Ras–ERK signalling pathway after various mitogenic stimulations. In mice, Spred proteins are identified as regulators of bone morphogenesis, hematopoietic processes, allergen‐induced airway eosinophilia and hyperresponsiveness. They inhibit cell motility and metastasis and have a high potential as tumor markers and suppressors of carcinogenesis. Moreover, in vertebrates, XtSpreds help together (...) with XtSprouty proteins to coordinate gastrulation and mesoderm specification. Here, we give an overview of this new field and summarize the domain functions, binding partners, expression patterns and the cellular localizations, regulations and functions of Spred proteins and try to give perspectives for future scientific directions. BioEssays 29:897–907, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

In the minds of many, Hox gene null mutant phenotypes have confirmed the direct role that these genes play in specifying the pattern of vertebrate embryos. The genes are envisaged as defining discrete spatial domains and, subsequently, conferring specific segmental identities on cells undergoing differentiation along the antero‐posterior axis. However, several aspects of the observed mutant phenotypes are inconsistent with this view. These include: the appearance of other, unexpected transformations along the dorsal axis; the occurrence of mirror‐image duplications; and the (...) development of anomalies outside the established domains of normal Hox gene expression. In this paper, Hox gene disruptions are shown to elicit regeneration‐like responses in tissues confronted with discontinuities in axial identity. The polarities and orientations of transformed segments which emerge as a consequence of this response obey the rules of distal transformation and intercalary regeneration. In addition, the incidence of periodic anomalies suggests that the initial steps of Hox‐mediated patterning occurs in Hensen's node. As gastrulation proceeds, mesoderm cell cycle kinetics impose constraints upon subsequent cellular differentiation. This results in the delayed manifestation of transformations along the antero‐posterior axis. Finally, a paradigm is sketched in which temporal, rather than spatial axial determinants direct differentiation. Specific, testable predictions are made about the role of Hox genes in the establishment of segmental identity. (shrink)

The mode and timing of germ-cell specification has been studied in diverse organisms, however, the molecular mechanism regulating germ-cell-fate determination remains to be elucidated. In some model organisms, maternal germ-cell determinants play a key role. In mouse embryos, some germ-line-specific gene products exist as maternal molecules and play critical roles in a pluripotential cell population at preimplantation stages. From those cells, primordial germ cells (PGCs) are specified by extracellular signaling mediated by tissue, as well as cell–cell interaction during gastrulation. (...) Thus, establishment of germ-cell lineage in mammalian embryos appears to be regulated by a multistep process, including formation and maintenance of a pluripotential cell population, as well as specification of PGCs. PGCs can be generated from pluripotential embryonic stem (ES) cells in a simple monolayer culture in which tissue interaction does not occur. This raises the possibility that ES cells, as well as, possibly, pluripotential cells in preimplantation embryos, are more closely related to the PGC precursors than pluripotential cells after implantation. BioEssays 27:136–143, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The origin of marine invertebrate larvae has been an area of controversy in developmental evolution for over a century. Here, we address the question of whether a pelagic “larval” or benthic “adult” morphology originated first in metazoan lineages by testing the hypothesis that particular gene co-option patterns will be associated with the origin of feeding, indirect developing larval forms. Empirical evidence bearing on this hypothesis is derivable from gene expression studies of the sea urchin larval gut of two closely related (...) but differently developing congenerics, Heliocidaris tuberculata (feeding indirect-developing larva) and H. erythrogramma (nonfeeding direct developer), given two subsidiary hypotheses. (1) If larval gut gene expression in H. tuberculata was co-opted from an ancestral adult expression pattern, then the gut expression pattern will remain in adult H. erythrogramma despite its direct development. (2) Genes expressed in the larval gut of H. tuberculata will not have a coordinated expression pattern in H. erythrogramma larvae due to loss of a functional gut. Five structural genes expressed in the invaginating archenteron of H. tuberculata during gastrulation exhibit substantially different expression patterns in H. erythrogramma with only one remaining endoderm specific. Expression of these genes in the adult of H. erythrogramma and larval gut of H. tuberculata, but not in H. erythrogramma larval endoderm, supports the hypothesis that they first played roles in the formation of adult structures and were subsequently recruited into larval ontogeny during the origin and evolution of feeding planktotrophic deuterostome larvae. (shrink)

The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage during the (...) Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. (shrink)

New research demonstrates that mechanics can serve as a means of information propagation in developing embryos. Historically, the study of embryonic development has had a dichotomy between morphogens and pattern formation on the one hand and morphogenesis and mechanics on the other. Secreted signals are the preeminent means of information propagation between cells and used to control cell fate, while physical forces act downstream or in parallel to shape tissue morphogenesis. However, recent work has blurred this division of function by (...) demonstrating that mechanics can serve as a means of information propagation. Adhesive or repulsive interactions can propagate through a tissue as a wave. These waves are rapid and directional and can be used to control the flux of cells through a developmental trajectory. Here, two examples are reviewed in which mechanics both guides and mediates morphogenesis and two examples in which mechanics intertwines with morphogens to regulate cell fate. (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)

American biologists in the late nineteenth century pioneered the descriptive-comparative study of all cell divisions from zygote to gastrulation -- the cell lineage. Data from cell lineages were crucial to evolutionary and developmental questions of the day. One of the main questions was the ultimate causation of developmental patterns -- historical or mechanical. E. B. Wilson's groundbreaking lineage work on the polychaete worm Nereis in 1892 set the stage for (1) an attack on Haeckel's phylogenetic-historical notion of recapitulation and (...) (2) support for mechanistic explanations of cleavage patterns. As more lineage work -- especially Lillie's work on "Unio" and Conklin's on "Crepidula" -- became available in the mid-late 1890s, mechanism was tempered with more evolutionary, homology-based views. However, as I show by focusing on three major issues -- homology, body plans and life history -- these views were primarily based on the precocious segregation and prospective significance -- what the cell became not what it was. Even on issues like adaptation, most lineagists argued teleologically from the adult backward. Most cell lineage workers, by 1900, were to varying degrees mechanist/experimentalist and recapitulationist simultaneously. The exception was E. G. Conklin, whose views were more akin to a Darwinian evolutionist than either mechanist or recapitulationist. Lineage work eventually declined and by 1907 published accounts of new lineages had basically stopped. I argue that established workers and younger researchers stopped wanting to take on cell lineage projects because the general patterns were the same for all the spiralians while the specifics showed too much variation. It was hard to theoretically encompass or analyze the minutiae of variation in a recapitulationist or mechanist framework. The only established worker who continued to do comparative lineage studies was E. G. Conklin, perhaps because the variation could best be accommodated by Darwinian evolution. (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)

Organismal form arises by the coordinated movement, arrangement, and activity of cells. In metazoans, most morphogenetic programs that establish the recognizable body plan of any given species are initiated during the developmental period, although in many species growth continues throughout life. By comparing the cellular and molecular development of the bilaterians (bilaterally symmetrical animals) to the development of their closest outgroup, the cnidarians, it appears that morphogenesis and the cell fate specification associated with germ layer formation during the process of (...) gastrulation are separately controlled by two distinct downstream pathways (canonical and planar cell polarity) of Wnt signaling. Furthermore, a fundamental change in the early developmental program, the positioning of the site of gastrulation, allowed the spatial separation of gene regulatory networks that facilitated the rapid diversification of bilaterian body plans. (shrink)