TGFbeta receptor saxophone non-autonomously regulates germline proliferation in a Smox/dSmad2-dependent manner in Drosophila testis.
Elucidating the regulatory mechanism of cell proliferation is central to the understanding of cancer development or organ size control. Drosophila spermatogenesis provides an excellent model to study cell proliferation since the germline cells mitotically amplify in a precise manner. However, the underlying molecular mechanism remains elusive. Germ cells derived from each gonialblast develop synchronously as one unit encapsulated by two somatic support cells (called cyst cells). Components of TGFbeta pathway have previously been found to restrict germ cell proliferation via their functions in cyst cells. Here we report that saxophone (sax), a TGFbeta type I receptor, is required in somatic cells to prevent the mitotically dividing spermatogonia from over-amplifying. Using various approaches, we demonstrate that Mad (Mothers against Dpp), a receptor-Smad usually associated with Sax-mediated TGFbeta/BMP signaling, is dispensable in this process. Instead, Smox (Smad on X, Drosophila Smad2), the other receptor-Smad formerly characterized in TGFbeta/activin signaling, is necessary for the precise mitotic divisions of spermatogonia. Furthermore, over-expressing Smox in cyst cells can partially rescue the proliferation phenotype induced by sax mutation. We propose that Smox acts downstream of Sax to prevent spermatogonial over-proliferation in Drosophila.
Li
Chun-Yan
CY
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences. Datun Road, Beijing 100101, PR China.
Guo
Zheng
Z
Wang
Zhaohui
Z
D000818:Animals; D049109:Cell Proliferation; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D009154:Mutation; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology
D029721:Drosophila Proteins; D018125:Receptors, Transforming Growth Factor beta; D051896:Smad Proteins, Receptor-Regulated; C115826:Smox protein, Drosophila; D016212:Transforming Growth Factor beta; C086338:sax protein, Drosophila