The conserved misshapen-warts-yorkie pathway acts in enteroblasts to regulate intestinal stem cells in drosophila

Qi Li, Shuangxi Li, Sebastian Mana-Capelli, Rachel J. RothFlach, Laura V. Danai, Alla Amcheslavsky, Yingchao Nie, Satoshi Kaneko, Xiaohao Yao, Xiaochu Chen, Jennifer L. Cotton, Junhao Mao, Dannel McCollum, Jin Jiang, Michael P. Czech, Lan Xu, Y. Tony Ip

Research output: Contribution to journalArticle

68 Scopus citations

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 thatthe 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.

Original languageEnglish (US)
Pages (from-to)291-304
Number of pages14
JournalDevelopmental cell
Volume31
Issue number3
DOIs
StatePublished - Nov 10 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Li, Q., Li, S., Mana-Capelli, S., RothFlach, R. J., Danai, L. V., Amcheslavsky, A., Nie, Y., Kaneko, S., Yao, X., Chen, X., Cotton, J. L., Mao, J., McCollum, D., Jiang, J., Czech, M. P., Xu, L., & Ip, Y. T. (2014). The conserved misshapen-warts-yorkie pathway acts in enteroblasts to regulate intestinal stem cells in drosophila. Developmental cell, 31(3), 291-304. https://doi.org/10.1016/j.devcel.2014.09.012