SRY AND THE TESTIS - MOLECULAR PATHWAYS OF ORGANOGENESIS

The gene Sry acts as a switch, initiating pathways leading to the diff erentiation of a testis rather than an ovary from the indifferent gona d (genital ridge) in mammals. The early events following Sry expressio n include rapid changes in the topographical organization of cells in the XY gonad. Sry must therefore initiate signaling pathways that dire ct male-specific patterns of proliferation, migration, cell-cell organ ization, and vascularization. We have identified an increase in male-s pecific proliferation by 12.0 days post coitum, while proliferation in the female gonad declines. We have also observed male-specific cell m igration from the mesonephros into the gonad in a composite organ cult ure system in which gonads from wild-type mice (CD1) and mesonephroi f rom a transgenic strain expressing beta-galactosidase in all its cells (ROSA26) were grafted together in vitro at the indifferent stage of g onadogenesis. Migration depends on an active signal that requires the presence of a Y chromosome in the gonadal portion of the graft. The si gnals that trigger migration operate over considerable distances, sugg esting either a long-range diffusible factor or the involvement of a r apid and efficient relay mechanism. Identification of the somatic cell s contributed from the mesonephros with cell-specific markers indicate d that some of the migrating cells were endothelial, revealing differe nces in processes of vascularization between male and female gonads. A second distinct population of migrating cells lay in close apposition to endothelial cells, and a third population occupied positions circu mscribing areas of condensing Sertoli cells. (C) 1998 Wiley-Liss, Inc.