Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 7 December 2001:
Vol. 294. no. 5549, pp. 2155 - 2158
DOI: 10.1126/science.1065718
Prev | Table of Contents | Next

Reports

Requirement of Math1 for Secretory Cell Lineage Commitment in the Mouse Intestine

Qi Yang,1 Nessan A. Bermingham,24 Milton J. Finegold,3 Huda Y. Zoghbi124*

The mouse small intestinal epithelium consists of four principal cell types deriving from one multipotent stem cell: enterocytes, goblet, enteroendocrine, and Paneth cells. Previous studies showed that Math1, a basic helix-loop-helix (bHLH) transcription factor, is expressed in the gut. We find that loss of Math1 leads to depletion of goblet, enteroendocrine, and Paneth cells without affecting enterocytes. Colocalization of Math1 with Ki-67 in some proliferating cells suggests that secretory cells (goblet, enteroendocrine, and Paneth cells) arise from a common progenitor that expresses Math1, whereas absorptive cells (enterocytes) arise from a progenitor that is Math1-independent. The continuous rapid renewal of these cells makes the intestinal epithelium a model system for the study of stem cell regeneration and lineage commitment.

1 Department of Pediatrics and Program in Developmental Biology,
2 Department of Molecular and Human Genetics,
3 Department of Pathology and
4 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
*   To whom correspondence should be addressed. E-mail: hzoghbi{at}bcm.tmc.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Review: Enteroendocrine cells: Neglected players in gastrointestinal disorders?.
G. W. Moran, F. C. Leslie, S. E. Levison, and J. T. McLaughlin (2008)
Therapeutic Advances in Gastroenterology 1, 51-60
   Abstract »    PDF »
Requirement of the Tissue-Restricted Homeodomain Transcription Factor Nkx6.3 in Differentiation of Gastrin-Producing G Cells in the Stomach Antrum.
M. Y. Choi, A. I. Romer, Y. Wang, M. P. Wu, S. Ito, A. B. Leiter, and R. A. Shivdasani (2008)
Mol. Cell. Biol. 28, 3208-3218
   Abstract »    Full Text »    PDF »
Myeloid Translocation Gene Family Members Associate with T-Cell Factors (TCFs) and Influence TCF-Dependent Transcription.
A. C. Moore, J. M. Amann, C. S. Williams, E. Tahinci, T. E. Farmer, J. A. Martinez, G. Yang, K. S. Luce, E. Lee, and S. W. Hiebert (2008)
Mol. Cell. Biol. 28, 977-987
   Abstract »    Full Text »    PDF »
The Adenocarcinoma-Associated Antigen, AGR2, Promotes Tumor Growth, Cell Migration, and Cellular Transformation.
Z. Wang, Y. Hao, and A. W. Lowe (2008)
Cancer Res. 68, 492-497
   Abstract »    Full Text »    PDF »
Mash1 is required for neuroendocrine cell development in the glandular stomach..
H. Kokubu, T. Ohtsuka, and R. Kageyama (2008)
Genes Cells 13, 41-51
   Abstract »    Full Text »    PDF »
Evolution of sensory structures in basal metazoa.
D. K. Jacobs, N. Nakanishi, D. Yuan, A. Camara, S. A. Nichols, and V. Hartenstein (2007)
Integr. Comp. Biol. 47, 712-723
   Abstract »    Full Text »    PDF »
Enteroendocrine precursors differentiate independently of Wnt and form serotonin expressing adenomas in response to active beta-catenin.
Y. Wang, M. Giel-Moloney, G. Rindi, and A. B. Leiter (2007)
PNAS 104, 11328-11333
   Abstract »    Full Text »    PDF »
Notch Signaling in Development and Cancer.
V. Bolos, J. Grego-Bessa, and J. L. de la Pompa (2007)
Endocr. Rev. 28, 339-363
   Abstract »    Full Text »    PDF »
The Hes gene family: repressors and oscillators that orchestrate embryogenesis.
R. Kageyama, T. Ohtsuka, and T. Kobayashi (2007)
Development 134, 1243-1251
   Abstract »    Full Text »    PDF »
Regulation of Cdx2 expression by promoter methylation, and effects of Cdx2 transfection on morphology and gene expression of human esophageal epithelial cells.
T. Liu, X. Zhang, C.-K. So, S. Wang, P. Wang, L. Yan, R. Myers, Z. Chen, A. P. Patterson, C. S. Yang, et al. (2007)
Carcinogenesis 28, 488-496
   Abstract »    Full Text »    PDF »
Rapid expansion of intestinal secretory lineages following a massive small bowel resection in mice.
M. A. Helmrath, J. J. Fong, C. M. Dekaney, and S. J. Henning (2007)
Am J Physiol Gastrointest Liver Physiol 292, G215-G222
   Abstract »    Full Text »    PDF »
Gata4 Is Essential for the Maintenance of Jejunal-Ileal Identities in the Adult Mouse Small Intestine.
T. Bosse, C. M. Piaseckyj, E. Burghard, J. J. Fialkovich, S. Rajagopal, W. T. Pu, and S. D. Krasinski (2006)
Mol. Cell. Biol. 26, 9060-9070
   Abstract »    Full Text »    PDF »
Canonical notch signaling functions as a commitment switch in the epidermal lineage..
C. Blanpain, W. E. Lowry, H. A. Pasolli, and E. Fuchs (2006)
Genes & Dev. 20, 3022-3035
   Abstract »    Full Text »    PDF »
Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment.
J. A. Clark, S. M. Doelle, M. D. Halpern, T. A. Saunders, H. Holubec, K. Dvorak, S. A. Boitano, and B. Dvorak (2006)
Am J Physiol Gastrointest Liver Physiol 291, G938-G949
   Abstract »    Full Text »    PDF »
A dynamic expression survey identifies transcription factors relevant in mouse digestive tract development.
M. Y. Choi, A. I. Romer, M. Hu, M. Lepourcelet, A. Mechoor, A. Yesilaltay, M. Krieger, P. A. Gray, and R. A. Shivdasani (2006)
Development 133, 4119-4129
   Abstract »    Full Text »    PDF »
HATH1 Expression in Mucinous Cancers of the Colorectum and Related Lesions..
E. T. Park, H. K. Oh, J. R. Gum Jr., S. C. Crawley, S. Kakar, J. Engel, C. C. Leow, W.-Q. Gao, and Y. S. Kim (2006)
Clin. Cancer Res. 12, 5403-5410
   Abstract »    Full Text »    PDF »
The Zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells.
M. S. Gierl, N. Karoulias, H. Wende, M. Strehle, and C. Birchmeier (2006)
Genes & Dev. 20, 2465-2478
   Abstract »    Full Text »    PDF »
Signals from Embryonic Fibroblasts Induce Adult Intestinal Epithelial Cells to Form Nestin-Positive Cells with Proliferation and Multilineage Differentiation Capacity In Vitro.
C. Wiese, A. Rolletschek, G. Kania, A. Navarrete-Santos, S. V. Anisimov, B. Steinfarz, K. V. Tarasov, S. A. Brugh, I. Zahanich, C. Ruschenschmidt, et al. (2006)
Stem Cells 24, 2085-2097
   Abstract »    Full Text »    PDF »
Mutant neurogenin-3 in congenital malabsorptive diarrhea..
J. Wang, G. Cortina, S. V. Wu, R. Tran, J.-H. Cho, M.-J. Tsai, T. J. Bailey, M. Jamrich, M. E. Ament, W. R. Treem, et al. (2006)
N. Engl. J. Med. 355, 270-280
   Abstract »    Full Text »    PDF »
Immune control of food intake: enteroendocrine cells are regulated by CD4+ T lymphocytes during small intestinal inflammation.
J R McDermott, F C Leslie, M D'Amato, D G Thompson, R K Grencis, and J T McLaughlin (2006)
Gut 55, 492-497
   Abstract »    Full Text »    PDF »
The proneural gene ascl1a is required for endocrine differentiation and cell survival in the zebrafish adenohypophysis.
H.-M. Pogoda, S. von der Hardt, W. Herzog, C. Kramer, H. Schwarz, and M. Hammerschmidt (2006)
Development 133, 1079-1089
   Abstract »    Full Text »    PDF »
Effects of a {gamma}-secretase inhibitor in a randomized study of patients with Alzheimer disease.
E. R. Siemers, J. F. Quinn, J. Kaye, M. R. Farlow, A. Porsteinsson, P. Tariot, P. Zoulnouni, J. E. Galvin, D. M. Holtzman, D. S. Knopman, et al. (2006)
Neurology 66, 602-604
   Abstract »    Full Text »    PDF »
Profile of Huda Y. Zoghbi.
R. Nuzzo (2006)
PNAS 103, 3017-3019
   Full Text »    PDF »
The Related Retinoblastoma (pRb) and p130 Proteins Cooperate to Regulate Homeostasis in the Intestinal Epithelium.
K. Haigis, J. Sage, J. Glickman, S. Shafer, and T. Jacks (2006)
J. Biol. Chem. 281, 638-647
   Abstract »    Full Text »    PDF »
Mtgr1 Is a Transcriptional Corepressor That Is Required for Maintenance of the Secretory Cell Lineage in the Small Intestine.
J. M. Amann, B. J. I. Chyla, T. C. Ellis, A. Martinez, A. C. Moore, J. L. Franklin, L. McGhee, S. Meyers, J. E. Ohm, K. S. Luce, et al. (2005)
Mol. Cell. Biol. 25, 9576-9585
   Abstract »    Full Text »    PDF »
A Role for Hath1, a bHLH Transcription Factor, in Colon Adenocarcinoma.
C. C. LEOW, P. POLAKIS, and W.-Q. GAO (2005)
Ann. N.Y. Acad. Sci. 1059, 174-183
   Abstract »    Full Text »    PDF »
Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation.
N. F. Shroyer, D. Wallis, K. J.T. Venken, H. J. Bellen, and H. Y. Zoghbi (2005)
Genes & Dev. 19, 2412-2417
   Abstract »    Full Text »    PDF »
Gastrointestinal Stem Cells. II. Intestinal stem cells.
M. Bjerknes and H. Cheng (2005)
Am J Physiol Gastrointest Liver Physiol 289, G381-G387
   Abstract »    Full Text »    PDF »
Direct regulation of intestinal fate by Notch.
B. Z. Stanger, R. Datar, L. C. Murtaugh, and D. A. Melton (2005)
PNAS 102, 12443-12448
   Abstract »    Full Text »    PDF »
Notch signaling regulates the differentiation of post-mitotic intestinal epithelial cells.
V. Zecchini, R. Domaschenz, D. Winton, and P. Jones (2005)
Genes & Dev. 19, 1686-1691
   Abstract »    Full Text »    PDF »
Regulation of Neuroendocrine Differentiation in Gastrointestinal Carcinoid Tumor Cells by Notch Signaling.
E. K. Nakakura, V. R. Sriuranpong, M. Kunnimalaiyaan, E. C. Hsiao, K. E. Schuebel, M. W. Borges, N. Jin, B. J. Collins, B. D. Nelkin, H. Chen, et al. (2005)
J. Clin. Endocrinol. Metab. 90, 4350-4356
   Abstract »    Full Text »    PDF »
Wnt signaling in the intestinal epithelium: from endoderm to cancer.
A. Gregorieff and H. Clevers (2005)
Genes & Dev. 19, 877-890
   Abstract »    Full Text »    PDF »
Altered Epithelial Cell Lineage Allocation and Global Expansion of the Crypt Epithelial Stem Cell Population Are Associated with Ileitis in SAMP1/YitFc Mice.
A. Vidrich, J. M. Buzan, S. Barnes, B. K. Reuter, K. Skaar, C. Ilo, F. Cominelli, T. Pizarro, and S. M. Cohn (2005)
Am. J. Pathol. 166, 1055-1067
   Abstract »    Full Text »    PDF »
Self-Renewal and Cancer of the Gut: Two Sides of a Coin.
F. Radtke and H. Clevers (2005)
Science 307, 1904-1909
   Abstract »    Full Text »    PDF »
Delta-Notch signalling controls commitment to a secretory fate in the zebrafish intestine.
C. Crosnier, N. Vargesson, S. Gschmeissner, L. Ariza-McNaughton, A. Morrison, and J. Lewis (2005)
Development 132, 1093-1104
   Abstract »    Full Text »    PDF »
Epithelial Stem Cells and Their Niche: There's No Place Like Home.
A. Z. Rizvi and M. H. Wong (2005)
Stem Cells 23, 150-165
   Abstract »    Full Text »    PDF »
Aberrant Expression of Human Achaete-Scute Homologue Gene 1 in the Gastrointestinal Neuroendocrine Carcinomas.
T. Shida, M. Furuya, T. Nikaido, T. Kishimoto, K. Koda, K. Oda, Y. Nakatani, M. Miyazaki, and H. Ishikura (2005)
Clin. Cancer Res. 11, 450-458
   Abstract »    Full Text »    PDF »
Insights into developmental mechanisms and cancers in the mammalian intestine derived from serial analysis of gene expression and study of the hepatoma-derived growth factor (HDGF).
M. Lepourcelet, L. Tou, L. Cai, J.-i. Sawada, A. J. F. Lazar, J. N. Glickman, J. A. Williamson, A. D. Everett, M. Redston, E. A. Fox, et al. (2005)
Development 132, 415-427
   Abstract »    Full Text »    PDF »
Modulation of Notch Processing by {gamma}-Secretase Inhibitors Causes Intestinal Goblet Cell Metaplasia and Induction of Genes Known to Specify Gut Secretory Lineage Differentiation.
J. Milano, J. McKay, C. Dagenais, L. Foster-Brown, F. Pognan, R. Gadient, R. T. Jacobs, A. Zacco, B. Greenberg, and P. J. Ciaccio (2004)
Toxicol. Sci. 82, 341-358
   Abstract »    Full Text »    PDF »
Id2 Drives Differentiation and Suppresses Tumor Formation in the Intestinal Epithelium.
R. G. Russell, A. Lasorella, L. E. Dettin, and A. Iavarone (2004)
Cancer Res. 64, 7220-7225
   Abstract »    Full Text »    PDF »
Mucin Is Produced by Clara Cells in the Proximal Airways of Antigen-Challenged Mice.
C. M. Evans, O. W. Williams, M. J. Tuvim, R. Nigam, G. P. Mixides, M. R. Blackburn, F. J. DeMayo, A. R. Burns, C. Smith, S. D. Reynolds, et al. (2004)
Am. J. Respir. Cell Mol. Biol. 31, 382-394
   Abstract »    Full Text »    PDF »
Hath1, Down-Regulated in Colon Adenocarcinomas, Inhibits Proliferation and Tumorigenesis of Colon Cancer Cells.
C. C. Leow, M. S. Romero, S. Ross, P. Polakis, and W.-Q. Gao (2004)
Cancer Res. 64, 6050-6057
   Abstract »    Full Text »    PDF »
Genomic Structure and Characterization of the 5'-Flanking Region of the Human Ghrelin Gene.
N. Kanamoto, T. Akamizu, T. Tagami, Y. Hataya, K. Moriyama, K. Takaya, H. Hosoda, M. Kojima, K. Kangawa, and K. Nakao (2004)
Endocrinology 145, 4144-4153
   Abstract »    Full Text »    PDF »
STEM CELL IN GASTROINTESTINAL STRUCTURE AND NEOPLASTIC DEVELOPMENT.
M Brittan and N A Wright (2004)
Gut 53, 899-910
   Full Text »    PDF »
Minireview: Development and Differentiation of Gut Endocrine Cells.
S. E. Schonhoff, M. Giel-Moloney, and A. B. Leiter (2004)
Endocrinology 145, 2639-2644
   Abstract »    Full Text »    PDF »
Functional diversity of notch family genes in fetal lung development.
Y. Kong, J. Glickman, M. Subramaniam, A. Shahsafaei, K. P. Allamneni, J. C. Aster, J. Sklar, and M. E. Sunday (2004)
Am J Physiol Lung Cell Mol Physiol 286, L1075-L1083
   Abstract »    Full Text »    PDF »
Expression of Notch Receptors and Ligands in the Adult Gut.
G. R. Sander and B. C. Powell (2004)
J. Histochem. Cytochem. 52, 509-516
   Abstract »    Full Text »    PDF »
Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway.
R. Gazit, V. Krizhanovsky, and N. Ben-Arie (2004)
Development 131, 903-913
   Abstract »    Full Text »    PDF »
Adipsin, a Biomarker of Gastrointestinal Toxicity Mediated by a Functional {gamma}-Secretase Inhibitor.
G. H. Searfoss, W. H. Jordan, D. O. Calligaro, E. J. Galbreath, L. M. Schirtzinger, B. R. Berridge, H. Gao, M. A. Higgins, P. C. May, and T. P. Ryan (2003)
J. Biol. Chem. 278, 46107-46116
   Abstract »    Full Text »    PDF »
From The Cover: Generation of hair cells by stepwise differentiation of embryonic stem cells.
H. Li, G. Roblin, H. Liu, and S. Heller (2003)
PNAS 100, 13495-13500
   Abstract »    Full Text »    PDF »
nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish.
A. N. Mayer and M. C. Fishman (2003)
Development 130, 3917-3928
   Abstract »    Full Text »    PDF »
Canonical Wnt signals are essential for homeostasis of the intestinal epithelium.
D. Pinto, A. Gregorieff, H. Begthel, and H. Clevers (2003)
Genes & Dev. 17, 1709-1713
   Abstract »    Full Text »    PDF »
Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis.
D. R. Linden, J.-X. Chen, M. D. Gershon, K. A. Sharkey, and G. M. Mawe (2003)
Am J Physiol Gastrointest Liver Physiol 285, G207-G216
   Abstract »    Full Text »    PDF »
The bHLH protein Dimmed controls neuroendocrine cell differentiation in Drosophila.
R. S. Hewes, D. Park, S. A. Gauthier, A. M. Schaefer, and P. H. Taghert (2003)
Development 130, 1771-1781
   Abstract »    Full Text »    PDF »
Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells.
A. Suzuki, H. Nakauchi, and H. Taniguchi (2003)
PNAS 100, 5034-5039
   Abstract »    Full Text »    PDF »
The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination.
P. Chen, J. E. Johnson, H. Y. Zoghbi, and N. Segil (2003)
Development 129, 2495-2505
   Abstract »    Full Text »    PDF »
Molecular features of adult mouse small intestinal epithelial progenitors.
T. S. Stappenbeck, J. C. Mills, and J. I. Gordon (2003)
PNAS 100, 1004-1009
   Abstract »    Full Text »    PDF »
Acidomucin goblet cell expansion induced by parenteral nutrition in the small intestine of piglets.
J. E. Conour, D. Ganessunker, K. A. Tappenden, S. M. Donovan, and H. R. Gaskins (2002)
Am J Physiol Gastrointest Liver Physiol 283, G1185-G1196
   Abstract »    Full Text »    PDF »
A Gene Expression Profile That Defines Colon Cell Maturation in Vitro.
J. M. Mariadason, D. Arango, G. A. Corner, M. J. Aranes, K. A. Hotchkiss, W. Yang, and L. H. Augenlicht (2002)
Cancer Res. 62, 4791-4804
   Abstract »    Full Text »    PDF »
Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity.
C. S. Lee, N. Perreault, J. E. Brestelli, and K. H. Kaestner (2002)
Genes & Dev. 16, 1488-1497
   Abstract »    Full Text »    PDF »
The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon.
J. P. Katz, N. Perreault, B. G. Goldstein, C. S. Lee, P. A. Labosky, V. W. Yang, and K. H. Kaestner (2002)
Development 129, 2619-2628
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)