Molecular mechanisms of development of the gastrointestinal tract

The gut offers a complex but rich organ system to study visceral pattern formation. The gut is an early evolutionary advance. Data supports that the molecular controls of gut pattern formation are be conserved across species. The gut develops in a stereotyped manner in many different species, by using a basic mechanism of development, the epithelial‐mesenchymal interaction. Signaling between the endoderm and mesoderm is essential for normal gut development. The signaling molecules involved are just being described and include factors known to be critical in embryonic development of other systems. The gut has four major patterned axes: anterior‐posterior (AP), dorsal‐ventral (DV), left‐right (LR), and radial (RAD). The molecular pathways used to control pattern in each of these axes are the subject of this review. Major advances in the understanding of AP and LR axis formation in the gut have been described within the past few years. RAD and DV axes are now hot topics for investigation. Despite advances in these areas of gut development, basic events remain poorly understood. Discovery of specific factors that control gut pattern formation may provide a template for the study of pattern formation in other visceral/organ systems. © 2000 Wiley‐Liss, Inc.

[1]  C. Tabin,et al.  Epithelial-mesenchymal signaling during the regionalization of the chick gut. , 1998, Development.

[2]  Andrew P. McMahon,et al.  Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity , 1993, Cell.

[3]  R. L. Parsons,et al.  Carcinoma of the colon following ureterosigmoidostomy: report of a case. , 1970, The Journal of urology.

[4]  M. Rosenfeld,et al.  Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis , 1999, Nature.

[5]  M. Mercola,et al.  An inductive role for the endoderm in Xenopus cardiogenesis. , 1995, Development.

[6]  M. Martindale,et al.  Expression patterns of anterior Hox genes in the polychaete Chaetopterus: correlation with morphological boundaries. , 2000, Developmental biology.

[7]  X. Zhu,et al.  Combined BMP-2 and FGF-4, but neither factor alone, induces cardiogenesis in non-precardiac embryonic mesoderm. , 1996, Developmental biology.

[8]  J. R. Coleman,et al.  Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. , 1996, Genes & development.

[9]  T. Jessell,et al.  Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord , 1994, Cell.

[10]  C. Nüsslein-Volhard,et al.  no tail (ntl) is the zebrafish homologue of the mouse T (Brachyury) gene. , 1994, Development.

[11]  J. Cooke,et al.  Left/right patterning signals and the independent regulation of different aspects of situs in the chick embryo. , 1997, Developmental biology.

[12]  D. Mortlock,et al.  Mutation of HOXA13 in hand-foot-genital syndrome , 1997, Nature Genetics.

[13]  M. Kedinger,et al.  Mesenchyme-dependent differentiation of epithelial progenitor cells in the gut. , 1987, Journal of pediatric gastroenterology and nutrition.

[14]  A. McMahon,et al.  Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. , 1995, Developmental biology.

[15]  K. Chawengsaksophak,et al.  Homeobox genes and gut development , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[16]  M. Tessier-Lavigne,et al.  Patterning of mammalian somites by surface ectoderm and notochord: Evidence for sclerotome induction by a hedgehog homolog , 1994, Cell.

[17]  N. Copeland,et al.  Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. , 1995, Genomics.

[18]  J. I. Izpisúa Belmonte,et al.  Knowing left from right: the molecular basis of laterality defects. , 2000, Molecular medicine today.

[19]  C. Tabin,et al.  Developmental biology: BMP signalling specifies the pyloric sphincter , 1999, Nature.

[20]  K. Zaret,et al.  Developmental competence of the gut endoderm: genetic potentiation by GATA and HNF3/fork head proteins. , 1999, Developmental biology.

[21]  P. Chambon,et al.  Gene dosage-dependent effects of the Hoxa-13 and Hoxd-13 mutations on morphogenesis of the terminal parts of the digestive and urogenital tracts. , 1997, Development.

[22]  R. Maas,et al.  Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. , 1996, Development.

[23]  J. Rossant,et al.  The transcription factor HNF3beta is required in visceral endoderm for normal primitive streak morphogenesis. , 1998, Development.

[24]  P. Ingham,et al.  A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos , 1993, Cell.

[25]  T. Mizuno,et al.  Gland formation induced in the allantoic and small-intestinal endoderm by the proventricular mesenchyme is not coupled with pepsinogen expression , 1985 .

[26]  R. Maas,et al.  Sexually dimorphic sterility phenotypes in HoxalO-deficient mice , 1995, Nature.

[27]  P. Ingham,et al.  Regulation of left-right asymmetries in the zebrafish by Shh and BMP4. , 1999, Developmental biology.

[28]  T. Takano,et al.  Spatial pattern of smooth muscle differentiation is specified by the epithelium in the stomach of mouse embryo , 1998, Developmental dynamics : an official publication of the American Association of Anatomists.

[29]  K Sigrist,et al.  GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. , 1997, Genes & development.

[30]  Wnt-3a regulates somite and tailbud formation in the mouse embryo. , 1994 .

[31]  W. Talbot,et al.  The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. , 1997, Development.

[32]  E. Morrisey,et al.  GATA-5: a transcriptional activator expressed in a novel temporally and spatially-restricted pattern during embryonic development. , 1997, Developmental biology.

[33]  M. Cohn,et al.  Fins, limbs, and tails: outgrowths and axial patterning in vertebrate evolution , 1998 .

[34]  M. Bienz,et al.  Homeotic gene expression in the visceral mesoderm of Drosophila embryos. , 1989, The EMBO journal.

[35]  E. Olson,et al.  GATA4: a novel transcriptional regulator of cardiac hypertrophy? , 1997, Circulation.

[36]  C. Tabin,et al.  The Transcription Factor Pitx2 Mediates Situs-Specific Morphogenesis in Response to Left-Right Asymmetric Signals , 1998, Cell.

[37]  H. Iba,et al.  BMPs are necessary for stomach gland formation in the chicken embryo: a study using virally induced BMP-2 and Noggin expression. , 2000, Development.

[38]  C. Tabin,et al.  Sonic hedgehog mediates the polarizing activity of the ZPA , 1993, Cell.

[39]  S. Henning Development of the gastrointestinal tract , 1986, The Proceedings of the Nutrition Society.

[40]  M. Kessel,et al.  FGF8 functions in the specification of the right body side of the chick , 1999, Current Biology.

[41]  T. Kameda,et al.  The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium. , 2000, Development.

[42]  B. Livingston,et al.  Characterization of a gene encoding a developmentally regulated winged helix transcription factor of the sea urchin Strongylocentrotus purpuratus. , 1999, Gene.

[43]  P. Ekblom,et al.  Tenascin during gut development: appearance in the mesenchyme, shift in molecular forms, and dependence on epithelial-mesenchymal interactions [published erratum appears in J Cell Biol 1989 Mar;108(3):following 1175] , 1988, The Journal of cell biology.

[44]  D. Warburton,et al.  TTF-1 regulates lung epithelial morphogenesis. , 1995, Developmental biology.

[45]  P. Beachy,et al.  Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function , 1996, Nature.

[46]  D. Melton,et al.  Endoderm development: from patterning to organogenesis. , 2000, Trends in genetics : TIG.

[47]  H. Takeda,et al.  Early Determination of Developmental Fate in Presumptive Intestinal Endoderm of the Chicken Embryo , 1991, Development, growth & differentiation.

[48]  A. Kuroiwa,et al.  Coordinated expression of Abd-B subfamily genes of the HoxA cluster in the developing digestive tract of chick embryo. , 1995, Developmental biology.

[49]  C. Tabin,et al.  Ectopic expression of Sonic hedgehog alters dorsal-ventral patterning of somites , 1994, Cell.

[50]  D. Duboule,et al.  Function of posterior HoxD genes in the morphogenesis of the anal sphincter. , 1996, Development.

[51]  D. Duboule,et al.  Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. , 1991, The EMBO journal.

[52]  A. Sater,et al.  Features of embryonic induction. , 1988, Development.

[53]  T. Schlange,et al.  The homeobox gene it NKX3.2 is a target of left–right signalling and is expressed on opposite sides in chick and mouse embryos , 1999, Current Biology.

[54]  J. Lough,et al.  Endoderm and heart development , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[55]  D. Witte,et al.  Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. , 1995, Development.

[56]  D. Duboule,et al.  Hox genes and the making of sphincters , 1999, Nature.

[57]  A. Moorman,et al.  Restriction of lactase gene expression along the proximal-to-distal axis of rat small intestine occurs during postnatal development. , 1994, Gastroenterology.

[58]  B. Hogan,et al.  PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. , 1996, Development.

[59]  M. Kedinger,et al.  Epithelial-mesenchymal interactions in intestinal epithelial differentiation. , 1988, Scandinavian journal of gastroenterology. Supplement.

[60]  C. Hunter,et al.  Hox gene expression in a single Caenorhabditis elegans cell is regulated by a caudal homolog and intercellular signals that inhibit wnt signaling. , 1999, Development.

[61]  Thomas M. Jessell,et al.  The winged-helix transcription factor HNF-3β is required for notochord development in the mouse embryo , 1994, Cell.

[62]  C. Tabin,et al.  Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. , 1995, Development.

[63]  H. Edlund,et al.  Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas , 1997, Current Biology.

[64]  S. Karam Lineage commitment and maturation of epithelial cells in the gut. , 1999, Frontiers in bioscience : a journal and virtual library.

[65]  C. Tickle,et al.  HOX-4 genes and the morphogenesis of mammalian genitalia. , 1991, Genes & development.

[66]  M. Levin Left‐right asymmetry in vertebrate embryogenesis , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[67]  M. Pankratz,et al.  Control of epithelial morphogenesis by cell signaling and integrin molecules in the Drosophila foregut. , 1995, Development.

[68]  M. Mercola,et al.  The compulsion of chirality: toward an understanding of left-right asymmetry. , 1998, Genes & development.

[69]  E. Olson,et al.  Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. , 1997, Genes & development.

[70]  S. Yasugi,et al.  In vitro analysis of mesenchymal influences on the differentiation of stomach epithelial cells of the chicken embryo. , 1999, Differentiation; research in biological diversity.

[71]  M. Kedinger,et al.  Smooth muscle actin expression during rat gut development and induction in fetal skin fibroblastic cells associated with intestinal embryonic epithelium. , 1990, Differentiation; research in biological diversity.

[72]  M. Scott,et al.  Conservation in hedgehog signaling: induction of a chicken patched homolog by Sonic hedgehog in the developing limb. , 1996, Development.

[73]  M. Kedinger,et al.  Inductive properties of fibroblastic cell cultures derived from rat intestinal mucosa on epithelial differentiation. , 1982, Differentiation; research in biological diversity.

[74]  A. Gossler,et al.  The Danforth's short tail mutation acts cell autonomously in notochord cells and ventral hindgut endoderm. , 1997, Development.

[75]  J. Rossant,et al.  The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. , 1993, Development.

[76]  I. Kirsch,et al.  The SIL gene is required for mouse embryonic axial development and left–right specification , 1999, Nature.

[77]  S. Yasugi Regulation of pepsinogen gene expression in epithelial cells of vertebrate stomach during development. , 1994, The International journal of developmental biology.

[78]  S. Yasugi Role of Epithelial‐Mesenchymal Interactions in Differentiation of Epithelium of Vertebrate Digestive Organs , 1993, Development, growth & differentiation.

[79]  H. Edlund,et al.  The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. , 1996, Development.

[80]  S. Noji,et al.  Sonic hedgehog expression in developing chicken digestive organs is regulated by epithelial–mesenchymal interactions , 1998, Development, growth & differentiation.

[81]  R. Maxson,et al.  SpHbox7, a new Abd‐B class homeobox gene from the sea urchin Strongylocentrotus purpuratus: Insights into the evolution of hox gene expression and function , 1996, Developmental dynamics : an official publication of the American Association of Anatomists.

[82]  C. Tabin,et al.  A molecular pathway determining left-right asymmetry in chick embryogenesis , 1995, Cell.

[83]  R. Lauro,et al.  The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. , 1991, Development.

[84]  R. Beddington,et al.  Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos. , 1994, The International journal of developmental biology.

[85]  R. Markwald,et al.  Formation and early morphogenesis of endocardial endothelial precursor cells and the role of endoderm. , 1996, Developmental biology.

[86]  A. McMahon,et al.  Sonic hedgehog regulates branching morphogenesis in the mammalian lung , 1998, Current Biology.

[87]  M. Nirenberg,et al.  Drosophila NK-homeobox genes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[88]  D. Melton,et al.  Vertebrate endoderm development. , 1999, Annual review of cell and developmental biology.

[89]  C. Killian,et al.  Spfkh1 encodes a transcription factor implicated in gut formation during sea urchin development , 1997, Development, growth & differentiation.

[90]  H. Saiga,et al.  Mesenchymal regulation of epithelial gene expression in developing avian stomach: 5'-flanking region of pepsinogen gene can mediate mesenchymal influence on its expression. , 1994, Development.

[91]  M. Kedinger,et al.  Fetal endoderm primarily holds the temporal and positional information required for mammalian intestinal development , 1994, The Journal of cell biology.

[92]  K. Kaestner,et al.  Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. , 1993, Development.

[93]  H. Westphal,et al.  Sonic hedgehog is essential to foregut development , 1998, Nature Genetics.

[94]  C. Mueller,et al.  GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. , 1994, The Journal of biological chemistry.

[95]  C H Fox,et al.  The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. , 1996, Genes & development.

[96]  J. Lough,et al.  Anterior endoderm is a specific effector of terminal cardiac myocyte differentiation of cells from the embryonic heart forming region , 1994, Developmental Dynamics.

[97]  D. Wilson,et al.  Wild-type endoderm abrogates the ventral developmental defects associated with GATA-4 deficiency in the mouse. , 1997, Developmental biology.

[98]  F. Segal,et al.  A CHARACTERIZATION OF FIBRANT SEGAL CATEGORIES , 2006, math/0603400.

[99]  H. Hauri,et al.  Fetal gut mesenchyme induces differentiation of cultured intestinal endodermal and crypt cells. , 1986, Developmental biology.

[100]  T. Mizuno,et al.  Pepsinogen gene transcription induced in heterologous epithelial-mesenchymal recombinations of chicken endoderms and glandular stomach mesenchyme. , 1988, Development.

[101]  C. Tabin,et al.  The genetics of human limb development. , 1994, American journal of human genetics.