TGFbeta receptor saxophone non-autonomously regulates germline proliferation in a Smox/dSmad2-dependent manner in Drosophila testis

Dev Biol. 2007 Sep 1;309(1):70-7. doi: 10.1016/j.ydbio.2007.06.019. Epub 2007 Jul 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology*
  • Male
  • Mutation
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology*
  • Signal Transduction
  • Smad Proteins, Receptor-Regulated / genetics
  • Smad Proteins, Receptor-Regulated / metabolism*
  • Spermatogenesis / physiology
  • Testis / metabolism
  • Transforming Growth Factor beta / physiology


  • Drosophila Proteins
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins, Receptor-Regulated
  • Smox protein, Drosophila
  • Transforming Growth Factor beta
  • sax protein, Drosophila