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

Research output: Contribution to journalArticle


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


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.


Original languageEnglish
Pages (from-to)3829-34
Number of pages6
JournalNational Academy of Sciences. Proceedings
Issue number10
Publication statusPublished - 6 Mar 2007


  • p27, stem cells, hypomorphs, colon, A33