c-Myb is required for progenitor cell homeostasis in colonic crypts
- 6 March 2007
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (10), 3829-3834
- https://doi.org/10.1073/pnas.0610055104
Abstract
The colonic crypt is the functional unit of the colon mucosa with a central role in ion and water reabsorption. Under steady-state conditions, the distal colonic crypt harbors a single stem cell at its base that gives rise to highly proliferative progenitor cells that differentiate into columnar, goblet, and endocrine cells. The role of c-Myb in crypt homeostasis has not been elucidated. Here we have studied three genetically distinct hypomorphic c-myb mutant mouse strains, all of which show reduced colonic crypt size. The mutations target the key domains of the transcription factor: the DNA binding, transactivation, and negative regulatory domains. In vivo proliferation and cell cycle marker studies suggest that these mice have a progenitor cell proliferation defect mediated in part by reduced Cyclin E1 expression. To independently assess the extent to which c-myb is required for colonic crypt homeostasis we also generated a novel tissue-specific mouse model to allow the deletion of c-myb in adult colon, and using these mice we show that c-Myb is required for crypt integrity, normal differentiation, and steady-state proliferation.This publication has 29 references indexed in Scilit:
- Mutations in theMYB intron I regulatory sequence increase transcription in colon cancersGenes, Chromosomes and Cancer, 2006
- c-Myb a stem-progenitor cell regulator in multiple tissue compartmentsGrowth Factors, 2005
- Analysis of the Regulation of the A33 Antigen Gene Reveals Intestine-specific Mechanisms of Gene ExpressionOnline Journal of Public Health Informatics, 2002
- p27 Expression in Inflammatory Bowel Disease-Associated Neoplasia: Further Evidence of a Unique Molecular PathogenesisThe American Journal of Pathology, 1999
- Tumor suppression by p27Kip1 and p21Cip1 during chemically induced skin carcinogenesisOncogene, 1999
- p21 (WAF1/CIP1) Expression Is Induced in Newly Nondividing Cells in Diverse Epithelia and during Differentiation of the Caco-2 Intestinal Cell LineExperimental Cell Research, 1996
- A Syndrome of Multiorgan Hyperplasia with Features of Gigantism, Tumorigenesis, and Female Sterility in p27Kip1-Deficient MiceCell, 1996
- Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.The Journal of cell biology, 1992
- A functional c-myb gene is required for normal murine fetal hepatic hematopoiesisCell, 1991
- Expression of the c-myb proto-oncogene during cellular proliferationNature, 1986