title: The Fused/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response.
abstract: In the Drosophila ovary, germline stem cells (GSCs) are maintained primarily by bone morphogenetic protein (BMP) ligands produced by the stromal cells of the niche. This signaling represses GSC differentiation by blocking the transcription of the differentiation factor Bam. Remarkably, bam transcription begins only one cell diameter away from the GSC in the daughter cystoblasts (CBs). How this steep gradient of response to BMP signaling is formed has been unclear. Here, we show that Fused (Fu), a serine/threonine kinase that regulates Hedgehog, functions in concert with the E3 ligase Smurf to regulate ubiquitination and proteolysis of the BMP receptor Thickveins in CBs. This regulation generates a steep gradient of BMP activity between GSCs and CBs, allowing for bam expression on CBs and concomitant differentiation. We observed similar roles for Fu during embryonic development in zebrafish and in human cell culture, implying broad conservation of this mechanism.
authors.affiliation: Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Laixin
authors.initials: L
authors.lastname: Xia
authors.forename: Shunji
authors.initials: S
authors.lastname: Jia
authors.forename: Shoujun
authors.initials: S
authors.lastname: Huang
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Mu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Kan
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zheng
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Qinmiao
authors.initials: Q
authors.lastname: Sun
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
authors.forename: Dahua
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; C492378:Smurf protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C085770:fu protein, Drosophila; D017346:Protein Serine-Threonine Kinases