ScienceWeek

DEVELOPMENTAL BIOLOGY: ON CELL MOVEMENTS DURING GASTRULATION

The following points are made by Lilianna Solnica-Krezel (Current Biology 2005 15:R213):

1) Gastrulation is a fundamental process of animal embryogenesis that shapes the internal and external features of developing animals. Introduced by Haeckel, the term gastrulation is derived from the Greek word "gaster", meaning stomach or gut. It describes a set of morphogenetic processes that transform the relatively unstructured early embryo into a gastrula with three germ layers -- endoderm, mesoderm and ectoderm. Vertebrate embryos display a conserved body plan with an elongated rostrocaudal axis. Along the dorsoventral axis, the nervous system takes the most dorsal position, above the notochord flanked by bilateral somites, and the most ventral alimentary structures, including the gut.

2) Vertebrate gastrulation involves four evolutionarily conserved morphogenetic movements: internalization, epiboly, convergence and extension. Internalization brings cells of the prospective mesoderm and endoderm beneath the future ectoderm via the blastopore, an opening in the blastula, known as blastoderm margin in fish, and primitive streak in amniotes. Epiboly movements spread and thin germ layers during gastrulation, while concurrent convergence and extension movements narrow them mediolaterally, and elongate the embryo from head to tail. Gastrulation is preceded and accompanied by inductive processes that specify and pattern the germ layers. These inductive processes are in large part controlled by the Spemann-Mangold organizer (SMO, hereafter referred to as the organizer), the key embryonic signaling center, which is located in the dorsal or axial aspect of the blastopore [1]. Work from the past two decades has revealed a great deal of conservation in the mechanisms of cell fate specification [2-4]. However, it is less clear whether this conservation also extends to the morphogenetic processes of gastrulation, in particular when the highly distinct architecture of gastrulae from different vertebrate groups is considered.

3) The fertilized zygote contains all the instructions for its embryonic development in the zygotic genome and as maternally derived cytoplasmic substances. The relative contributions of zygotic and maternal regulation vary among vertebrates and this is reflected particularly in the speed and pattern of the early cleavages, and consequently in the morphology of the blastula. Fish and amphibian embryos develop externally and the fast rate of their early development ensures swift formation of independent larvae. These embryos rely on rich energy stores in the form of a yolk and on maternal determinants that mediate development until the midblastula stage, when the zygotic genome becomes transcriptionally active and takes control [5]. The yolk is generally concentrated vegetally and is either distributed between the blastomeres via complete cleavages, as in frog embryos, or deposited in a separate yolk cell, as seen in incompletely cleaving fish embryos. Consequently, the fish blastula is a mound of blastomeres at the animal region on top of a large syncytial yolk cell. By contrast, the frog blastula consists of smaller blastomeres at the animal hemisphere surrounding a blastocoel cavity and larger blastomeres in the vegetal region.

4) In summary: Vertebrate embryogenesis entails an exquisitely coordinated combination of cell proliferation, fate specification and movement. After induction of the germ layers, the blastula is transformed by gastrulation movements into a multilayered embryo with head, trunk and tail rudiments. Gastrulation is heralded by formation of a blastopore, an opening in the blastula. The axial side of the blastopore is marked by the organizer, a signaling center that patterns the germ layers and regulates gastrulation movements. During internalization, endoderm and mesoderm cells move via the blastopore beneath the ectoderm. Epiboly movements expand and thin the nascent germ layers. Convergence movements narrow the germ layers from lateral to medial while extension movements elongate them from head to tail. Despite different morphology, parallels emerge with respect to the cellular and genetic mechanisms of gastrulation in different vertebrate groups. Patterns of gastrulation cell movements relative to the blastopore and the organizer are similar from fish to mammals, and conserved molecular pathways mediate gastrulation movements.

References (abridged):

1. Spemann, H. Embryonic Development and Induction. (1938). Yale University Press, New Haven, CT

2. De Robertis, E.M., Larrain, J., Oelgeschlager, M., and Wessely, O. The establishment of Spemann's organizer and patterning of the vertebrate embryo. (2000). Nat. Rev. Genet. 1, 171-181

3. Niehrs, C. Regionally specific induction by the Spemann-Mangold organizer. (2004). Nat. Rev. Genet. 5, 425-434

4. Harland, R. and Gerhart, J. Formation and function of Spemann's organizer. (1997). Annu. Rev. Cell Dev. Biol. 13, 611-667

5. Newport, J. and Kirschner, M. A major developmental transition in early Xenopus embryos: II. Control of the onset of transcription. (1982). Cell 30, 687-696

Current Biology http://www.current-biology.com

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EVOLUTION: DEVELOPMENT AND EVOLUTION OF THE GUT

The following points are made by Didier Y. Stainier (Science 2005 307:1902):

1) At first glance, the gut looks deceptively simple: an epithelial tube composed of a few cell types and surrounded by an innervated muscle layer Yet in evolutionary terms, the gut, as an endodermal organ, predates any mesodermal organ, and it has reached a level of complexity and sophistication that is only starting to be appreciated. Gut formation is one of the first outcomes of multicellularity. Bringing cells together allowed the organism the opportunity to make specialized cell types, with selective pressure leading to the emergence of an outer protective coat (the ectoderm) and an inner layer (the endoderm) involved in food absorption. The mesoderm, or middle layer, arose approximately 40 million years after the emergence of the ectoderm and endoderm and was most probably a derivative of the latter. The originally simple aggregate of cells involved in food absorption has thus evolved into a very large and complex structure that is highly patterned in its longitudinal, dorsoventral, left-right, and radial axes.

2) Over the past decade or so, studies in a number of invertebrate and vertebrate model systems, including Caenorhabditis elegans, Drosophila, sea urchins, ascidians, Xenopus, zebrafish, the chick, and the mouse, have provided insights into the genes and cellular mechanisms regulating endoderm formation [1,2]. These studies have revealed a high degree of conservation in some of the transcriptional regulators of endoderm formation; for example, members of the Gata and Forkhead transcription factor families have been implicated in this process across the phyla, although the intercellular events regulating endoderm formation appear to be more divergent. The Wnt signaling pathway has been implicated in the formation of the endoderm in C. elegans, sea urchins, and ascidians, whereas transforming growth factor-beta (more specifically Nodal) signaling has been implicated in the formation of the endoderm in vertebrate embryos. However, this apparent lack of conservation of the signaling pathways regulating endoderm formation probably reflects our incomplete understanding of the process. Indeed, we have not yet gained sufficient knowledge to control the efficient differentiation of mammalian stem cells into endoderm, meaning that the investigation of endoderm formation must proceed using multiple approaches in multiple model systems.

3) As mentioned above, the mesoderm can be thought of, at some level, as a derivative of the endoderm and indeed, the endoderm and mesoderm often originate from the same or adjacent regions of the embryo. Although the mechanisms leading to the segregation of these two lineages are fairly well understood in C. elegans and sea urchins, for example, much remains to be learned about this process in vertebrates. Again, this knowledge will be necessary to enhance our ability to coax stem cells into various endodermal or mesodermal lineages.

4) In summary: The function of an organ is dependent on its cellular constituents as well as on their assembly into a cohesive unit. The developing gut faces unique challenges as one of the longest and largest organs in the body and also because it is constantly interfacing with external factors through the diet. Its location deep within the body has until recently hampered investigation into its formation. The patterning of the gut along its longitudinal, dorsoventral, left-right, and radial axes is one of the fascinating issues that pertain to the development, function, and homeostasis of this understudied organ.[3-5]

References (abridged):

1. D. Y. Stainier, Genes Dev. 16, 893 (2002)

2. D. Clements, M. Rex, H. R. Woodland, Int. Rev. Cytol. 203, 383 (2001)

3. M. Bienz, Trends Genet. 10, 22 (1994)

4. F. Beck, F. Tata, K. Chawengsaksophak, Bioessays 22, 431 (2000)

5. A. Grapin-Botton, D. A. Melton, Trends Genet. 16, 124 (2000)

Science http://www.sciencemag.org

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ON GUT FORMATION IN ANIMALS

The following points are made by B. Fuss and M. Hoch (Current Biology 2002 12:171):

1) The morphological processes involved in the development of the gastrointestinal tract of animals are highly similar. In mouse and chicken embryos, gut formation is initiated by the formation of two open-ended tubes at opposite sites of the embryo. The tubes are generated by the invagination of the endodermal layer in an anterior-ventral position and later in a posterior-ventral region. The gut tubes then grow and extend toward each other until they meet and fuse around the yolk stalk. In the fruit fly Drosophila, gut formation is also initiated with gastrulation by the invagination of cells of the anterior-ventral and posterior-dorsal region of the embryo to give rise to the foregut and hindgut primordial tubes, respectively. The midgut forms in between these tubes by fusion of an anterior and a posterior primordium. As the gut tubes form, visceral mesoderm is recruited to surround the invaginating gut epithelia.

2) The primitive gut tube of vertebrates and invertebrates is initially regionalized along the anterior-posterior axis into three broad domains: the foregut, the midgut, and the hindgut. Ultimately, these domains are further subdivided, and derived organs such as the lungs, pancreas, or liver in vertebrates, and the proventriculus or the Malpighian tubules in Drosophila, are specified. The similarity of the morphological processes during gut formation is paralleled by the function of evolutionarily conserved molecular regulators of gastrointestinal development.

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