The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila
Interdisciplinary Graduate Program
Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology; Department of Cancer Biology
Cell Biology | Developmental Biology
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.
DOI of Published Version
Dev Cell. 2014 Nov 10;31(3):291-304. doi: 10.1016/j.devcel.2014.09.012. Epub 2014 Nov 10. Link to article on publisher's site
Li, Qi; Mana-Capelli, Sebastian; Roth Flach, Rachel J.; Danai, Laura V.; Amcheslavsky, Alla; Nie, Yingchao; Kaneko, Satoshi; Yao, Xiaohao; Chen, Xiaochu; Cotton, Jennifer L.; Mao, Junhao; McCollum, Dannel; Czech, Michael P.; Xu, Lan; and Ip, Y. Tony, "The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila" (2014). GSBS Student Publications. 2020.