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

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

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.


Also Published In

Developmental Cell

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Academic Units
Pathology and Cell Biology
Published Here
January 3, 2020