| Literature DB >> 25453828 |
Qi Li1, Shuangxi Li2, Sebastian Mana-Capelli3, Rachel J Roth Flach1, Laura V Danai1, Alla Amcheslavsky1, Yingchao Nie1, Satoshi Kaneko1, Xiaohao Yao1, Xiaochu Chen1, Jennifer L Cotton4, Junhao Mao4, Dannel McCollum3, Jin Jiang2, Michael P Czech1, Lan Xu5, Y Tony Ip6.
Abstract
Similar to the mammalian intestine, the Drosophila adult midgut has resident stem cells that support growth and regeneration. How the niche regulates intestinal stem cell activity in both mammals and flies is not well understood. Here, we show that the conserved germinal center protein kinase Misshapen restricts intestinal stem cell division by repressing the expression of the JAK-STAT pathway ligand Upd3 in differentiating enteroblasts. Misshapen, a distant relative to the prototypic Warts activating kinase Hippo, interacts with and activates Warts to negatively regulate the activity of Yorkie and the expression of Upd3. The mammalian Misshapen homolog MAP4K4 similarly interacts with LATS (Warts homolog) and promotes inhibition of YAP (Yorkie homolog). Together, this work reveals that the Misshapen-Warts-Yorkie pathway acts in enteroblasts to control niche signaling to intestinal stem cells. These findings also provide a model in which to study requirements for MAP4K4-related kinases in MST1/2-independent regulation of LATS and YAP.Entities:
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Year: 2014 PMID： 25453828 PMCID： PMC4254555 DOI： 10.1016/j.devcel.2014.09.012
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270