A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster

Carole L.C. Poon, Weijie Liu, Yanjun Song, Marta Gomez, Yavuz Kulaberoglu, Xiaomeng Zhang, Wenjian Xu, Alexey Veraksa, Alexander Hergovich, Amin Ghabrial, Kieran F. Harvey

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Hippo-like pathways are ancient signaling modules first identified in yeasts. The best-defined metazoan module forms the core of the Hippo pathway, which regulates organ size and cell fate. Hippo-like kinase modules consist of a Sterile 20-like kinase, an NDR kinase, and non-catalytic protein scaffolds. In the Hippo pathway, the upstream kinase Hippo can be activated by another kinase, Tao-1. Here, we delineate a related Hippo-like signaling module that Tao-1 regulates to control tracheal morphogenesis in Drosophila melanogaster. Tao-1 activates the Sterile 20-like kinase GckIII by phosphorylating its activation loop, a mode of regulation that is conserved in humans. Tao-1 and GckIII act upstream of the NDR kinase Tricornered to ensure proper tube formation in trachea. Our study reveals that Tao-1 activates two related kinase modules to control both growth and morphogenesis. The Hippo-like signaling pathway we have delineated has a potential role in the human vascular disease cerebral cavernous malformation.

Original languageEnglish
Pages (from-to)564-575
Number of pages12
JournalDevelopmental Cell
Volume47
Issue number5
DOIs
Publication statusPublished - 3 Dec 2018

Keywords

  • Hippo-like pathways
  • kinases
  • morphogenesis
  • signaling
  • trachea
  • tubular networks

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