title: Nodal/activin signaling promotes male germ cell fate and suppresses female programming in somatic cells.
abstract: 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.
authors.affiliation: Department of Genetics, SOKENDAI, Yata 1111, Mishima 411-8540, Japan.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wu
authors.forename: Kohei
authors.initials: K
authors.lastname: Kanata
authors.forename: Rie
authors.initials: R
authors.lastname: Saba
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D051525:Fibroblast Growth Factor 9 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism; D055458:Left-Right Determination Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D055457:Nodal Protein / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins; D019849:Sex Determination Processes; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D051525:Fibroblast Growth Factor 9; D055458:Left-Right Determination Factors; C111386:Lefty1 protein, mouse; C526162:Lefty2 protein, mouse; C477341:Nanos2 protein, mouse; D055457:Nodal Protein; D016601:RNA-Binding Proteins; D028341:Activins