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Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3829-34. Epub 2007 Feb 26.

c-Myb is required for progenitor cell homeostasis in colonic crypts.

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1
Peter MacCallum Cancer Centre and Pathology Department, University of Melbourne, Melbourne VIC 8006, Australia.

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.

PMID:
17360438
PMCID:
PMC1820669
DOI:
10.1073/pnas.0610055104
[Indexed for MEDLINE]
Free PMC Article
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