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.

Malaterre, J., Carpinelli, M., Ernst, M., Alexander, W., Cooke, M., Sutton, S., et al. (2007). c-Myb is required for progenitor cell homeostasis in colonic crypts. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104(10), 3829-3834 [10.1073/pnas.0610055104].

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

CARPINELLI, Massimo;
2007

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.
Articolo in rivista - Articolo scientifico
A33; Colon; Hypomorphs; p27; Stem cells
English
3829
3834
6
Malaterre, J., Carpinelli, M., Ernst, M., Alexander, W., Cooke, M., Sutton, S., et al. (2007). c-Myb is required for progenitor cell homeostasis in colonic crypts. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104(10), 3829-3834 [10.1073/pnas.0610055104].
Malaterre, J; Carpinelli, M; Ernst, M; Alexander, W; Cooke, M; Sutton, S; Dworkin, S; Heath, J; Frampton, J; Mcarthur, G; Clevers, H; Hilton, D; Mantamadiotis, T; Ramsay, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/389647
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