|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 127, Issue 22 4905-4913, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
M Hebrok, SK Kim, B St Jacques, AP McMahon and DA Melton
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Pancreas organogenesis is regulated by the interaction of distinct signaling pathways that promote or restrict morphogenesis and cell differentiation. Previous work has shown that activin, a TGF(beta+) signaling molecule, permits pancreas development by repressing expression of Sonic hedgehog (Shh), a member of the hedgehog family of signaling molecules that antagonize pancreas development. Here we show that Indian hedgehog (Ihh), another hedgehog family member, and Patched 1 (Ptc1), a receptor and negative regulator of hedgehog activity, are expressed in pancreatic tissue. Targeted inactivation of Ihh in mice allows ectopic branching of ventral pancreatic tissue resulting in an annulus that encircles the duodenum, a phenotype frequently observed in humans suffering from a rare disorder known as annular pancreas. Shh(-)(/)(-) and Shh(-)(/)(-) Ihh(+/)(-) mutants have a threefold increase in pancreas mass, and a fourfold increase in pancreatic endocrine cell numbers. In contrast, mutations in Ptc1 reduce pancreas gene expression and impair glucose homeostasis. Thus, islet cell, pancreatic mass and pancreatic morphogenesis are regulated by hedgehog signaling molecules expressed within and adjacent to the embryonic pancreas. Defects in hedgehog signaling may lead to congenital pancreatic malformations and glucose intolerance.
This article has been cited by other articles:
|
|
 |
|
  M Mimeault and S K Batra Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer Gut, October 1, 2008; 57(10): 1456 - 1468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Varjosalo and J. Taipale Hedgehog: functions and mechanisms Genes & Dev., September 15, 2008; 22(18): 2454 - 2472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J King, L. Guasti, and E. Laufer Hedgehog signalling in endocrine development and disease J. Endocrinol., September 1, 2008; 198(3): 439 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Oliver-Krasinski and D. A. Stoffers On the origin of the {beta} cell Genes & Dev., August 1, 2008; 22(15): 1998 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Wade, P. Juneja, A. W. MacKay, J. Graham, P. J. Havel, L. H. Tecott, and E. H. Goulding Synergistic Impairment of Glucose Homeostasis in ob/ob Mice Lacking Functional Serotonin 2C Receptors Endocrinology, March 1, 2008; 149(3): 955 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. de Sauvage and J. C. Marsters Jr. The Hedgehog Signaling Pathway in Cancer ASCO Educational Book, January 1, 2008; 2008(1): e1 - e4. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Jorgensen, J. Ahnfelt-Ronne, J. Hald, O. D. Madsen, P. Serup, and J. Hecksher-Sorensen An Illustrated Review of Early Pancreas Development in the Mouse Endocr. Rev., October 1, 2007; 28(6): 685 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. van den Brink Hedgehog Signaling in Development and Homeostasis of the Gastrointestinal Tract Physiol Rev, October 1, 2007; 87(4): 1343 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Li, T. Yu, M. Morishima, A. Pao, J. LaDuca, J. Conroy, N. Nowak, S.-I. Matsui, I. Shiraishi, and Y. E. Yu Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities Hum. Mol. Genet., June 1, 2007; 16(11): 1359 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Mfopou, V. De Groote, X. Xu, H. Heimberg, and L. Bouwens Sonic Hedgehog and Other Soluble Factors from Differentiating Embryoid Bodies Inhibit Pancreas Development Stem Cells, May 1, 2007; 25(5): 1156 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ait-Lounis, D. Baas, E. Barras, C. Benadiba, A. Charollais, R. Nlend Nlend, D. Liegeois, P. Meda, B. Durand, and W. Reith Novel Function of the Ciliogenic Transcription Factor RFX3 in Development of the Endocrine Pancreas Diabetes, April 1, 2007; 56(4): 950 - 959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Simeone, L. Zhang, M. K. Treutelaar, L. Zhang, K. Graziano, C. D. Logsdon, and C. F. Burant Islet hypertrophy following pancreatic disruption of Smad4 signaling Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1305 - E1316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Giurgea, C. Sempoux, C. Bellanne-Chantelot, M. Ribeiro, L. Hubert, N. Boddaert, J.-M. Saudubray, J.-J. Robert, F. Brunelle, J. Rahier, et al. The Knudson's Two-Hit Model and Timing of Somatic Mutation May Account for the Phenotypic Diversity of Focal Congenital Hyperinsulinism J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4118 - 4123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Asayesh, J. Sharpe, R. P. Watson, J. Hecksher-Sorensen, N. D. Hastie, R. E. Hill, and U. Ahlgren Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1-/- mice. Genes & Dev., August 15, 2006; 20(16): 2208 - 2213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ta, Y. Choi, F. Atouf, C. H. Park, and N. Lumelsky The Defined Combination of Growth Factors Controls Generation of Long-Term-Replicating Islet Progenitor-Like Cells from Cultures of Adult Mouse Pancreas Stem Cells, July 1, 2006; 24(7): 1738 - 1749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Heiser, J. Lau, M. M. Taketo, P. L. Herrera, and M. Hebrok Stabilization of {beta}-catenin impacts pancreas growth Development, May 15, 2006; 133(10): 2023 - 2032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Sicklick, Y.-X. Li, A. Jayaraman, R. Kannangai, Y. Qi, P. Vivekanandan, J. W. Ludlow, K. Owzar, W. Chen, M. S. Torbenson, et al. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis Carcinogenesis, April 1, 2006; 27(4): 748 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Hruban, N. V. Adsay, J. Albores-Saavedra, M. R. Anver, A. V. Biankin, G. P. Boivin, E. E. Furth, T. Furukawa, A. Klein, D. S. Klimstra, et al. Pathology of Genetically Engineered Mouse Models of Pancreatic Exocrine Cancer: Consensus Report and Recommendations Cancer Res., January 1, 2006; 66(1): 95 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lu, T. Ventura-Holman, J. Li, R. W. McMurray, J. S. Subauste, and J. F. Maher Abnormal Glucose Homeostasis and Pancreatic Islet Function in Mice with Inactivation of the Fem1b Gene Mol. Cell. Biol., August 1, 2005; 25(15): 6570 - 6577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Perez, D. A. Cano, T. Dao-Pick, J.-P. Rougier, Z. Werb, and M. Hebrok Matrix Metalloproteinases 2 and 9 Are Dispensable for Pancreatic Islet Formation and Function In Vivo Diabetes, March 1, 2005; 54(3): 694 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Habener, D. M. Kemp, and M. K. Thomas Minireview: Transcriptional Regulation in Pancreatic Development Endocrinology, March 1, 2005; 146(3): 1025 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Haumaitre, E. Barbacci, M. Jenny, M. O. Ott, G. Gradwohl, and S. Cereghini Lack of TCF2/vHNF1 in mice leads to pancreas agenesis PNAS, February 1, 2005; 102(5): 1490 - 1495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Micallef, M. E. Janes, K. Knezevic, R. P. Davis, A. G. Elefanty, and E. G. Stanley Retinoic Acid Induces Pdx1-Positive Endoderm in Differentiating Mouse Embryonic Stem Cells Diabetes, February 1, 2005; 54(2): 301 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Wolf, H.-C. Kuo, K.-Y. F. Pau, and L. Lester Progress with Nonhuman Primate Embryonic Stem Cells Biol Reprod, December 1, 2004; 71(6): 1766 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gutierrez-Frias, R. Sacedon, C. Hernandez-Lopez, T. Cejalvo, T. Crompton, A. G. Zapata, A. Varas, and A. Vicente Sonic Hedgehog Regulates Early Human Thymocyte Differentiation by Counteracting the IL-7-Induced Development of CD34+ Precursor Cells J. Immunol., October 15, 2004; 173(8): 5046 - 5053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Cano, N. S. Murcia, G. J. Pazour, and M. Hebrok orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization Development, July 15, 2004; 131(14): 3457 - 3467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fagman, M. Grande, A. Gritli-Linde, and M. Nilsson Genetic Deletion of Sonic Hedgehog Causes Hemiagenesis and Ectopic Development of the Thyroid in Mouse Am. J. Pathol., May 1, 2004; 164(5): 1865 - 1872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. van Eyll, C. E. Pierreux, F. P. Lemaigre, and G. G. Rousseau Shh-dependent differentiation of intestinal tissue from embryonic pancreas by activin A J. Cell Sci., April 15, 2004; 117(10): 2077 - 2086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhu, T. Tran, J. M. Rukstalis, P. Sun, B. Damsz, and S. F. Konieczny Inhibition of Mist1 Homodimer Formation Induces Pancreatic Acinar-to-Ductal Metaplasia Mol. Cell. Biol., April 1, 2004; 24(7): 2673 - 2681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yoshitomi and K. S. Zaret Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a Development, February 15, 2004; 131(4): 807 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kawahira, N. H. Ma, E. S. Tzanakakis, A. P. McMahon, P.-T. Chuang, and M. Hebrok Combined activities of hedgehog signaling inhibitors regulate pancreas development Development, October 15, 2003; 130(20): 4871 - 4879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-e. Wang, J. Shou, S. Ross, H. Koeppen, F. J. de Sauvage, and W.-Q. Gao Inhibition of Epithelial Ductal Branching in the Prostate by Sonic Hedgehog Is Indirectly Mediated by Stromal Cells J. Biol. Chem., May 9, 2003; 278(20): 18506 - 18513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Aubin, U. Dery, M. Lemieux, P. Chailler, and L. Jeannotte Stomach regional specification requires Hoxa5-driven mesenchymal-epithelial signaling Development, September 1, 2002; 129(17): 4075 - 4087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Gustafsson, H. Pan, D. F. Pinney, Y. Liu, A. Lewandowski, D. J. Epstein, and C. P. Emerson Jr. Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification Genes & Dev., January 1, 2002; 16(1): 114 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bhushan, N. Itoh, S. Kato, J. P. Thiery, P. Czernichow, S. Bellusci, and R. Scharfmann Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis Development, December 15, 2001; 128(24): 5109 - 5117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Kim and M. Hebrok Intercellular signals regulating pancreas development and function Genes & Dev., January 15, 2001; 15(2): 111 - 127. [Full Text]
|
|
|
|
|
|
M. Dyer, S. Farrington, D Mohn, J. Munday, and M. Baron Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo Development, January 5, 2001; 128(10): 1717 - 1730. [Abstract] [PDF]
|
|
|
|
|
|
G Deutsch, J Jung, M Zheng, J Lora, and K. Zaret A bipotential precursor population for pancreas and liver within the embryonic endoderm Development, January 3, 2001; 128(6): 871 - 881. [Abstract] [PDF]
|
|
