Btk29A Promotes Wnt4 Signaling in the Niche to Terminate Germ Cell Proliferation in Drosophila

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Science  17 Jan 2014:
Vol. 343, Issue 6168, pp. 294-297
DOI: 10.1126/science.1244512

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Wnt–β-Catenin in Germ Cells

The Wnt–β-catenin pathway contributes to many signaling mechanisms during organismal development and carcinogenesis by regulating both transcription and cell adhesion. Hamada-Kawaguchi et al. (p. 294) demonstrate that this pathway must be activated in ovarian somatic cells to stop proliferation of germ cells in Drosophila. Phosphorylation of a tyrosine residue on β-catenin by the tyrosine kinase Btk turns on signaling in the niche cells by promoting transcriptional activity of β-catenin. Failure in this process resulted in ovarian tumors in the flies.


Btk29A is the Drosophila ortholog of the mammalian Bruton’s tyrosine kinase (Btk), mutations of which in humans cause a heritable immunodeficiency disease. Btk29A mutations stabilized the proliferating cystoblast fate, leading to an ovarian tumor. This phenotype was rescued by overexpression of wild-type Btk29A and phenocopied by the interference of Wnt4–β-catenin signaling or its putative downstream nuclear protein Piwi in somatic escort cells. Btk29A and mammalian Btk directly phosphorylated tyrosine residues of β-catenin, leading to the up-regulation of its transcriptional activity. Thus, we identify a transcriptional switch involving the kinase Btk29A/Btk and its phosphorylation target, β-catenin, which functions downstream of Wnt4 in escort cells to terminate Drosophila germ cell proliferation through up-regulation of piwi expression. This signaling mechanism likely represents a versatile developmental switch.

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