Abstract:
:The crucial role of individual Notch receptors and the mechanism by which they maintain intestinal crypt progenitor cells were assessed by using a series of inducible gut-specific Notch mutant mice. We found that Notch1 and Notch2 receptors function redundantly in the gut, as only simultaneous loss of both receptors results in complete conversion of proliferating crypt progenitors into post-mitotic goblet cells. This conversion correlates with the loss of Hes1 expression and derepression of the cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p57Kip2. We also found that the promoter of both CDK inhibitor genes is occupied by the Notch effector Hes1 in wild-type crypt progenitor cells. Thus, our results indicate that Notch-mediated Hes1 expression contributes to the maintenance of the proliferative crypt compartment of the small intestine by transcriptionally repressing two CDK inhibitors.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Riccio O,van Gijn ME,Bezdek AC,Pellegrinet L,van Es JH,Zimber-Strobl U,Strobl LJ,Honjo T,Clevers H,Radtke Fdoi
10.1038/embor.2008.7subject
Has Abstractpub_date
2008-04-01 00:00:00pages
377-83issue
4eissn
1469-221Xissn
1469-3178pii
embor20087journal_volume
9pub_type
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