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

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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

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Warts
Stem cells
Drosophila
Stem Cells
Long-Acting Thyroid Stimulator
Phosphotransferases
Mammals
Diptera
Cell Division
Protein Kinases
Intestines
Regeneration
Ligands
Growth

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Li, Q., Li, S., Mana-Capelli, S., RothFlach, R. J., Danai, L. V., Amcheslavsky, A., ... 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

The conserved misshapen-warts-yorkie pathway acts in enteroblasts to regulate intestinal stem cells in drosophila. / Li, Qi; Li, Shuangxi; Mana-Capelli, Sebastian; RothFlach, Rachel J.; Danai, Laura V.; Amcheslavsky, Alla; Nie, Yingchao; Kaneko, Satoshi; Yao, Xiaohao; Chen, Xiaochu; Cotton, Jennifer L.; Mao, Junhao; McCollum, Dannel; Jiang, Jin; Czech, Michael P.; Xu, Lan; Ip, Y. Tony.

In: Developmental Cell, Vol. 31, No. 3, 10.11.2014, p. 291-304.

Research output: Contribution to journalArticle

Li, Q, Li, S, Mana-Capelli, S, RothFlach, RJ, Danai, LV, Amcheslavsky, A, Nie, Y, Kaneko, S, Yao, X, Chen, X, Cotton, JL, Mao, J, McCollum, D, Jiang, J, Czech, MP, Xu, L & Ip, YT 2014, 'The conserved misshapen-warts-yorkie pathway acts in enteroblasts to regulate intestinal stem cells in drosophila', Developmental Cell, vol. 31, no. 3, pp. 291-304. https://doi.org/10.1016/j.devcel.2014.09.012
Li, Qi ; Li, Shuangxi ; Mana-Capelli, Sebastian ; RothFlach, Rachel J. ; Danai, Laura V. ; Amcheslavsky, Alla ; Nie, Yingchao ; Kaneko, Satoshi ; Yao, Xiaohao ; Chen, Xiaochu ; Cotton, Jennifer L. ; Mao, Junhao ; McCollum, Dannel ; Jiang, Jin ; Czech, Michael P. ; Xu, Lan ; Ip, Y. Tony. / The conserved misshapen-warts-yorkie pathway acts in enteroblasts to regulate intestinal stem cells in drosophila. In: Developmental Cell. 2014 ; Vol. 31, No. 3. pp. 291-304.
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