The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila.

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.
AuthorsQi Li, Shuangxi Li, Sebastian Mana-Capelli, Rachel J Roth Flach, 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
JournalDevelopmental cell (Dev Cell) Vol. 31 Issue 3 Pg. 291-304 (Nov 10 2014) ISSN: 1878-1551 [Electronic] United States
PMID25453828 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Drosophila Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Yorkie protein, Drosophila
  • Protein Kinases
  • misshapen protein, Drosophila
  • warts protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • Animals
  • Cell Differentiation (physiology)
  • Cell Division
  • Drosophila Proteins (metabolism)
  • Drosophila melanogaster (metabolism)
  • Intestines (metabolism)
  • Nuclear Proteins (metabolism)
  • Protein Kinases (metabolism)
  • Protein-Serine-Threonine Kinases (metabolism)
  • Regeneration (genetics, physiology)
  • Signal Transduction (physiology)
  • Stem Cells (cytology)
  • Trans-Activators (metabolism)

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