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

Jordane Malaterre, Marina Carpinelli, Matthias R Ernst, Warren Alexander, Michael P Cooke, Susan Sutton, Sebastian Dworkin, Joan K Heath, Jon Frampton, Grant McArthur, Hans Clevers, Douglas J Hilton, Theo Mantamadiotis, Robert G Ramsay

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83 Citations (Scopus)

Abstract

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. ? 2007 by The National Academy of Sciences of the USA.
Original languageEnglish
Pages (from-to)3829 - 3834
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number10
DOIs
Publication statusPublished - 2007

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