Nodal/activin signaling promotes male germ cell fate and suppresses female programming in somatic cells

Development. 2013 Jan 15;140(2):291-300. doi: 10.1242/dev.087882. Epub 2012 Dec 5.


Testicular development in the mouse is triggered in somatic cells by the function of Sry followed by the activation of fibroblast growth factor 9 (FGF9), which regulates testicular differentiation in both somatic and germ cells. However, the mechanism is unknown. We show here that the nodal/activin signaling pathway is activated in both male germ cells and somatic cells. Disruption of nodal/activin signaling drives male germ cells into meiosis and causes ectopic initiation of female-specific genes in somatic cells. Furthermore, we prove that nodal/activin-A works directly on male germ cells to induce the male-specific gene Nanos2 independently of FGF9. We conclude that nodal/activin signaling is required for testicular development and propose a model in which nodal/activin-A acts downstream of fibroblast growth factor signaling to promote male germ cell fate and protect somatic cells from initiating female differentiation.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / metabolism*
  • Animals
  • Carrier Proteins / metabolism
  • Cell Differentiation*
  • Female
  • Fibroblast Growth Factor 9 / metabolism
  • Gene Expression Regulation, Developmental*
  • Germ Cells / metabolism
  • Left-Right Determination Factors / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Nodal Protein / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA-Binding Proteins
  • Sex Determination Processes
  • Signal Transduction
  • Time Factors


  • Carrier Proteins
  • Fibroblast Growth Factor 9
  • Left-Right Determination Factors
  • Lefty1 protein, mouse
  • Lefty2 protein, mouse
  • Nanos2 protein, mouse
  • Nodal Protein
  • RNA-Binding Proteins
  • Activins