c-Myb is required for progenitor cell homeostasis in colonic crypts Academic Article uri icon

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.

authors

  • Malaterre, J
  • Carpinelli, M
  • Ernst, M
  • Alexander, W
  • Cooke, M
  • Sutton, S
  • Dworkin, S
  • Heath, JK
  • Frampton, J
  • McArthur, G
  • Clevers, H
  • Hilton, D
  • Mantamadiotis, T
  • Ramsay, RG

publication date

  • March 6, 2007