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JOURNAL ARTICLES
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
M.F. Offield, T.L. Jetton, P.A. Labosky, M. Ray, R.W. Stein, M.A. Magnuson, B.L. Hogan, C.V. Wright
Development 1996 122: 983-995;

Summary

It has been proposed that the Xenopus homeobox gene, XlHbox8, is involved in endodermal differentiation during pancreatic and duodenal development (Wright, C.V.E., Schnegelsberg, P. and De Robertis, E.M. (1988). Development 105, 787–794). To test this hypothesis directly, gene targeting was used to make two different null mutations in the mouse XlHbox8 homolog, pdx-1. In the first, the second pdx-1 exon, including the homeobox, was replaced by a neomycin resistance cassette. In the second, a lacZ reporter was fused in-frame with the N terminus of PDX-1, replacing most of the homeodomain. Neonatal pdx-1 −/− mice are apancreatic, in confirmation of previous reports (Jonsson, J., Carlsson, L., Edlund, T. and Edlund, H. (1994). Nature 371, 606–609). However, the pancreatic buds do form in homozygous mutants, and the dorsal bud undergoes limited proliferation and outgrowth to form a small, irregularly branched, ductular tree. This outgrowth does not contain insulin or amylase-positive cells, but glucagon-expressing cells are found. The rostral duodenum shows a local absence of the normal columnar epithelial lining, villi, and Brunner's glands, which are replaced by a GLUT2-positive cuboidal epithelium resembling the bile duct lining. Just distal of the abnormal epithelium, the numbers of enteroendocrine cells in the villi are greatly reduced. The PDX-1/beta-galactosidase fusion allele is expressed in pancreatic and duodenal cells in the absence of functional PDX-1, with expression continuing into perinatal stages with similar boundaries and expression levels. These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors.

Reference

    1. Bonnerot C.,
    2. Nicolas J.
    (1993) Application of LacZ gene fusions to postimplantation development. Meth. Enz 225, 451–469
    OpenUrlCrossRefPubMedWeb of Science
    1. Camper S. A.,
    2. Saunders T. L.,
    3. Katz R. W.,
    4. Reeves R. H.
    (1990) The Pit-1 transcription factor gene is a candidate for the murine Snell dwarf mutation. Genomics 8, 586–590
    OpenUrlCrossRefPubMedWeb of Science
    1. Cohn S.,
    2. Simon T.,
    3. Roth K.,
    4. Birkenmeier E.,
    5. Gordon J.
    (1992) Use of transgenic mice to map cis -acting elements in the Intestinal Fatty Acid Binding Protein Gene (Fabpi) that control its cell lineage-specific and regional patterns of expression along the duodenal-colonic and crypt-villus axes of the gut epithelium. J. Cell Biol 119, 27–44
    OpenUrlAbstract/FREE Full Text
    1. Dear T.N.,
    2. Colledge W.H.,
    3. Carlton M.B.L.,
    4. Lavenir I.,
    5. Larson T.,
    6. Smith A.J.H.,
    7. Warren A.J.,
    8. Evans M.J.,
    9. Sofroniew M.V.,
    10. Rabbitts T.H.
    (1995) The Hox11 gene is essential for cell survival during spleen development. Development 121, 2909–2915
    OpenUrlAbstract
    1. Fitzpatrick V. D.,
    2. Percival-Smith A.,
    3. Ingles C. J.,
    4. Krause H. M.
    (1992) Homeodomain-independent activity of the fushi-tarazu polypeptide in Drosophila embryos. Nature 356, 610–612
    OpenUrlCrossRefPubMed
    1. Gehring W. J.,
    2. Qian Y. Q.,
    3. Billeter M.,
    4. Furukubo-Tokunaga K.,
    5. Schier A. F.,
    6. Resendez-Perez D.,
    7. Affolter M.,
    8. Otting G.,
    9. Wuthrich K.
    (1994) Homeodomain-DNA recognition. Cell 78, 211–223
    OpenUrlCrossRefPubMedWeb of Science
    1. Golosow N.,
    2. Grobstein C.
    (1962) Epitheliomesenchymal interaction in pancreatic morphogenesis. Dev. Biol 4, 242–255
    OpenUrlCrossRefPubMedWeb of Science
    1. Guz Y.,
    2. Montminy M. R.,
    3. Stein R.,
    4. Leonard J.,
    5. Gamer L. W.,
    6. Wright C. V.,
    7. Teitelman G.
    (1995) Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium, and pancreatic exocrine and endocrine progenitors during ontogeny. Development 121, 11–18
    OpenUrlAbstract
    1. Jetton T. L.,
    2. Liang Y.,
    3. Pettipher C. C.,
    4. Zimmerman E. C.,
    5. Cox F. G.,
    6. Horvath K.,
    7. Matschinsky F. M.,
    8. Magnuson M.
    (1994) Analysis of upstream glucokinase promoter activity in transgenic mice and identification of glucokinase in rare neuroendocrine cells in the brain and gut. J. Biol. Chem 269, 3641–3654
    OpenUrlAbstract/FREE Full Text
    1. Jonsson. J.,
    2. Carlsson L.,
    3. Edlund T.,
    4. Edlund H.
    (1994) Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371, 606–609
    OpenUrlCrossRefPubMedWeb of Science
    1. Krumlauf R.
    (1994) Hox genes in vertebrate development. Cell 78, 191–201
    OpenUrlCrossRefPubMedWeb of Science
    1. Le Douarin N. M.
    (1975) An experimental analysis of liver development. Medical Biology 53, 427–455
    OpenUrlPubMedWeb of Science
    1. Leonard J.,
    2. Peers B.,
    3. Johnson T.,
    4. Ferreri K.,
    5. Lee S.,
    6. Montminy M. R.
    (1993) Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells. Mol. Endocrinol 7, 1275–1283
    OpenUrlCrossRefPubMedWeb of Science
    1. Li S.,
    2. Crenshaw E. B., 3rd.,
    3. Rawson E. J.,
    4. Simmons D. M.,
    5. Swanson L. W.,
    6. Rosenfeld M. G.
    (1990) Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature 347, 528–533
    OpenUrlCrossRefPubMedWeb of Science
    1. McGinnis W.
    (1994) A century of homeosis, a decade of homeoboxes. Genetics 3, 607–611
    OpenUrl
    1. Miller C. P.,
    2. McGehee R. E., Jr.,
    3. Habener J. F.
    (1994) IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. EMBO J 13, 1145–1156
    OpenUrlPubMedWeb of Science
    1. Murphy P.,
    2. Hill R. E.
    (1991). Expression of the mouse labial -like homeobox-containing genes, Hox 2.9 and Hox 1.6, during segmentation of the hindbrain. Development 111, 61–74
    OpenUrlAbstract
    1. Ohlsson H.,
    2. Karlsson K.,
    3. Edlund T.
    (1993) IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J 12, 4251–4259
    OpenUrlPubMedWeb of Science
    1. Pang K.,
    2. Mukonoweshuro C.,
    3. Wong G. G.
    (1994) Beta cells arise from glucose transporter type 2 (Glut2)-expressing epithelial cells of the developing rat pancreas. Proc. Natl. Acad. Sci. USA 91, 9559–9563
    OpenUrlAbstract/FREE Full Text
    1. Peers B.,
    2. Leonard J.,
    3. Sharma S.,
    4. Teitelman G.,
    5. Montminy M. R.
    (1994) Insulin expression in pancreatic islet cells relies on cooperative interactions between the helix loop helix factor E47 and the homeobox factor STF-1. Mol. Endocrinol 8, 1798–1806
    OpenUrlCrossRefPubMedWeb of Science
    1. Peshavaria M.,
    2. Gamer L.,
    3. Henderson E.,
    4. Teitelman G.,
    5. Wright C.,
    6. Stein R.
    (1994) XlHbox 8, an endoderm-specific Xenopus homeodomain protein, is closely related to a mammalian insulin gene transcription factor. Mol. Endocrinol 8, 806–816
    OpenUrlCrossRefPubMedWeb of Science
    1. Roberts C. W.,
    2. Shutter J. R.,
    3. Korsmeyer S. J.
    (1994) Hox11 controls the genesis of the spleen. Nature 368, 747–749
    OpenUrlCrossRefPubMed
    1. Roth K. A.,
    2. Rubin D. C.,
    3. Birkenmeier E. H.,
    4. Gordon J. I.
    (1991) Expression of liver fatty acid-binding protein/human growth hormone fusion genes within the enterocyte and enteroendocrine cell populations of fetal transgenic mice. J. Biol. Chem 266, 5949–5954
    OpenUrlAbstract/FREE Full Text
    1. Scarpelli D. G.,
    2. Rao M. S.
    (1981) Differentiation of regenerating pancreatic cells into hepatocyte like cells. Proc. Natl. Acad. Sci. USA 78, 2577–2581
    OpenUrlAbstract/FREE Full Text
    1. Schneider-Maunoury S.,
    2. Topilko P.,
    3. Seitandou T.,
    4. Levi G.,
    5. Cohen-Tannoudji M.,
    6. Pournin S.,
    7. Babinet C.,
    8. Charnay P.
    (1993) Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Cell 75, 1199–1214
    OpenUrlCrossRefPubMedWeb of Science
    1. Shaw J. W.,
    2. Latimer E. O.
    (1926) Regeneration of pancreatic tissue from the transplanted pancreatic duct in the dog. Am. J. Physiol 76, 49–53
    OpenUrl
    1. Sweetser E.,
    2. Birkenmeier E. H.,
    3. Hoppe P. C.,
    4. McKeel D. W.,
    5. Gordon J. G.
    (1988) Mechanisms underlying generation of gradients in gene expression within the intestine: an analysis using transgenic mice containing fatty acid binding protein-human growth hormone fusion genes. Genes Dev 2, 1318–1332
    OpenUrlAbstract/FREE Full Text
    1. Teitelman G.,
    2. Alpert S.,
    3. Polak J. M.,
    4. Martinez A.,
    5. Hanahan D.
    (1993) Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide. Development 118, 1031–1039
    OpenUrlAbstract/FREE Full Text
    1. Thorens B.,
    2. Cheng Z.,
    3. Brown D.,
    4. Lodish H.
    (1990) Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells. Am. J. Physiol 259, 279–.
    OpenUrl
    1. Wessells N. K.,
    2. Cohen J. H.
    (1967) Early pancreas organogenesis: morphogenesis, tissue interactions, and mass effects. Dev. Biol 15, 237–270
    OpenUrlCrossRefPubMedWeb of Science
    1. Winnier G.,
    2. Blessing M.,
    3. Labosky P. A.,
    4. Hogan B. L. M.
    (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9, 2105–2116
    OpenUrlAbstract/FREE Full Text
    1. Wright C. V. E.,
    2. Schnegelsberg P.,
    3. De Robertis E. M.
    (1988) XlHbox 8: a novel Xenopus homeo protein restricted to a narrow band of endoderm. Development 105, 787–794
    OpenUrlAbstract/FREE Full Text
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JOURNAL ARTICLES
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
M.F. Offield, T.L. Jetton, P.A. Labosky, M. Ray, R.W. Stein, M.A. Magnuson, B.L. Hogan, C.V. Wright
Development 1996 122: 983-995;
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