Pdgfr-alpha mediates testis cord organization and fetal Leydig cell development in the XY gonad.
During testis development, the rapid morphological changes initiated by Sry require the coordinate integration of many signaling pathways. Based on the established role of the platelet-derived growth factor (PDGF) family of ligands and receptors in migration, proliferation, and differentiation of cells in various organ systems, we have investigated the role of PDGF in testis organogenesis. Analysis of expression patterns and characterization of the gonad phenotype in Pdgfr-alpha(-/-) embryos identified PDGFR-alpha as a critical mediator of signaling in the early testis at multiple steps of testis development. Pdgfr-alpha(-/-) XY gonads displayed disruptions in the organization of the vasculature and in the partitioning of interstitial and testis cord compartments. Closer examination revealed severe reductions in characteristic XY proliferation, mesonephric cell migration, and fetal Leydig cell differentiation. This work identifies PDGF signaling through the alpha receptor as an important event downstream of Sry in testis organogenesis and Leydig cell differentiation.
Brennan
Jennifer
J
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Tilmann
Christopher
C
Capel
Blanche
B
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007985:Leydig Cells / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009154:Mutation; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000502:physiology*; D019849:Sex Determination Processes; D013737:Testis / Q000098:blood supply / Q000196:embryology*; D013997:Time Factors; D014960:X Chromosome; D014998:Y Chromosome
D008024:Ligands; D020796:Receptor, Platelet-Derived Growth Factor alpha; D001973:Bromodeoxyuridine