Trends in Genetics
Volume 16, Issue 3, 1 March 2000, Pages 124-130
Journal home page for Trends in Genetics

Review
Endoderm development: from patterning to organogenesis

https://doi.org/10.1016/S0168-9525(99)01957-5Get rights and content

Abstract

Although the ectoderm and mesoderm have been the focus of intensive work in the recent era of studies on the molecular control of vertebrate development, the endoderm has received less attention. Because signaling must occur between germ layers in order to achieve a properly organized body, our understanding of the coordinated development of all organs requires a more thorough consideration of the endoderm and its derivatives. This review focuses on present knowledge and perspectives concerning endoderm patterning and organogenesis. Some of the classical embryology of the endoderm is discussed and the progress and deficiencies in cellular and molecular studies are noted.

Section snippets

Formation of the gut tube

Although ectoderm and endoderm share the common feature of forming a tube from a flat sheet of cells, the way in which the tubes form is different. The neural tube arises from the apposition of two lateral ridges of ectoderm that close in an anterior to posterior direction, whereas the gut tube, in mouse and chicken embryos, forms from a crescent-shaped fold, the so-called anterior intestinal portal (AIP), which appears in the endoderm at the anterior tip of the embryo when somitogenesis

Gut organs have overlapping presumptive territories

Soon after the formation of the gut tube, the onset of organogenesis is revealed by the swelling, budding and coiling of specific regions. How organ formation correlates with specific regions of the flat endodermal sheet has been a recurrent question, asked as early as 1874 when His17 published a map of the presumptive digestive and respiratory organs of the chick blastoderm. More recently, fate-mapping experiments have traced the fate of cells in the definitive digestive organs in the chick7,

Budding organs off the main gut tube

The endoderm not only gives rise to the digestive tract but also to organs that branch from the main tube. These organs include, from anterior to posterior, the thyroid, parathyroids, thymus, ultimobranchial body, respiratory system, liver, gallbladder, pancreas and caecum (Fig. 4). Gland formation generally begins as a thickening of the epithelium. Epithelial cells then either remain connected by a duct, as for the liver, gallbladder and pancreas, or epithelial buds migrate away from the gut

Morphogenesis

After the position of each organ is defined, a complex cell choreography that involves variations in cell adhesion, mobility, attractive and repulsive cues as well as proliferation and cell death, shapes the organs.

Differentiation of cell types within the different regions

Markers of terminal differentiation are expressed prior to endoderm organ morphogenesis64 . For instance, expression of intestinal fatty acid binding protein (IFABP) is already observed at E7.5 in the mouse3 and glucagon-producing cells appear in the gut epithelium prior to the formation of the pancreatic bud3. Cells at this stage do not express the entire panel of differentiation genes required for their function in the adult and the meaning of this early differentiation is still obscure.

To

Conclusions

One can expect that the endoderm will receive increased attention in the next few years as researchers turn their attention to organogenesis and the genetic control of physiological function. Targeted mutations in mice will probably reveal many genes that specify cytodifferentiation in endodermal derivatives, as well as important information on cell lineages. From our embryological perspective, there are two key issues: (1) understanding how the gut tube is patterned to make different organs,

Acknowledgements

We regret citing reviews in many instances rather than the original publications owing to space constraints. We are grateful to J. Wells, M. Hebrok and M. Rhamalho Santos for helpful comments on the manuscript and to D. Procupez for her help with Fig. 1. A.G-B. was supported by fellowships from the Association Française pour la Recherche contre le Cancer and Human Frontier Science Program. Work in the authors’ laboratory is supported by the Howard Hughes Medical Institute and National

References (71)

  • J. Aubin

    Early postnatal lethality in Hoxa-5 mutant mice is attributable to respiratory tract defects

    Dev. Biol.

    (1997)
  • A.M. Boulet et al.

    Targeted disruption of hoxc-4 causes esophageal defects and vertebral transformations

    Dev. Biol.

    (1996)
  • B.L. Hogan

    Morphogenesis

    Cell

    (1999)
  • S. Dietrich et al.

    Undulated phenotypes suggest a role for Pax -1 for the development of vertebral and extravertebral structures

    Dev. Biol.

    (1995)
  • K. Zaret

    Early liver differentiation: genetic potentiation and multilevel growth control

    Curr. Opin. Genet. Dev.

    (1998)
  • J-P. Thiery

    Ontogenic expression of cell adhesion molecules: L-CAM is found in epithelia derived from the three primary germ layers

    Dev. Biol.

    (1984)
  • S.S. Chan

    UNC-40, a C. elegans homolog of DCC required in motile cells responding to UNC-6 netrin cues

    Cell

    (1996)
  • A. Apelqvist

    Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas

    Curr. Biol.

    (1997)
  • Y. Yokouchi

    Coordinated expression of Abd-B subfamily genes of the HoxA cluster in the developing digestive tract of chick embryo

    Dev. Biol.

    (1995)
  • G.L. Henry et al.

    Mixer, a homeobox gene required for endoderm development

    Science

    (1998)
  • J. Wells et al.

    Vertebrate endoderm development

    Annu. Rev. Cell Dev. Biol.

    (1999)
  • N. Le Douarin

    Etude experimentale de l’organogenése du tube digestif et du foie chez l’embryon de poulet

    Bull. Biol. Fr. Bel.

    (1964)
  • J.D. Molkentin

    Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis

    Genes Dev.

    (1997)
  • C.T. Kuo

    GATA4 transcription factor is required for ventral morphogenesis and heart tube formation

    Genes Dev.

    (1997)
  • K.P. Rehorn

    A molecular aspect of hematopoiesis and endoderm development common to vertebrates and Drosophila

    Development

    (1996)
  • G. Winnier

    Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse

    Genes Dev.

    (1995)
  • M.J. Solloway et al.

    Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup

    Development

    (1999)
  • A.J. Roebroek

    Failure of ventral closure and axial rotation in embryos lacking the proprotein convertase Furin

    Development

    (1998)
  • W. His

    Unsere Körperform und das Physiologishe Problem Ihrer Entstehung

    (1874)
  • S. Matsushita

    Fate mapping study of the endoderm of the 1.5-day-old chick embryo

    Roux’s Arch. Develop. Biol.

    (1996)
  • R.M. Warga et al.

    Origin and development of the Zebrafish endoderm

    Development

    (1999)
  • T.M. Schultheiss

    Induction of avian cardiac myogenesis by anterior endoderm

    Development

    (1995)
  • Y. Ishii

    Early specification of intestinal epithelium in the chicken embryo: a study on the localization and regulation of CdxA expression

    Dev. Growth Diff.

    (1997)
  • Y. Ishii

    Region-specific expression of chicken Sox2 in the developing gut and lung epithelium: regulation by epithelial–mesenchymal interactions

    Dev. Dyn.

    (1998)
  • S. Yasugi

    Role of epithelial–mesenchymal interactions in differentiation of epithelium of vertebrate digestive organs

    Dev. Growth Diff.

    (1993)
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