RESUMO
The initiation of de novo testis cord organization in the fetal gonad is poorly understood. Endothelial cell migration into XY gonads initiates testis morphogenesis. However, neither the signals that regulate vascularization of the gonad nor the mechanisms through which vessels affect tissue morphogenesis are known. Here, we show that Vegf signaling is required for gonad vascularization and cord morphogenesis. We establish that interstitial cells express Vegfa and respond, by proliferation, to endothelial migration. In the absence of vasculature, four-dimensional imaging of whole organs revealed that interstitial proliferation is reduced and prevents formation of wedge-like structures that partition the gonad into cord-forming domains. Antagonizing vessel maturation also reduced proliferation. However, proliferation of mesenchymal cells was rescued by the addition of PDGF-BB. These results suggest a pathway that integrates initiation of vascular development and testis cord morphogenesis, and lead to a model in which undifferentiated mesenchyme recruits blood vessels, proliferates in response, and performs a primary function in the morphogenesis and patterning of the developing organ.
Assuntos
Padronização Corporal/fisiologia , Endotélio Vascular/metabolismo , Mesoderma/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais/fisiologia , Testículo/embriologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Becaplermina , Movimento Celular/fisiologia , Primers do DNA/genética , Endotélio Vascular/fisiologia , Citometria de Fluxo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Proteínas Proto-Oncogênicas c-sis , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta-GalactosidaseRESUMO
Sexually dimorphic development of the gonad is essential for germ cell development and sexual reproduction. We have found that the Drosophila embryonic gonad is already sexually dimorphic at the time of initial gonad formation. Male-specific somatic gonadal precursors (msSGPs) contribute only to the testis and express a Drosophila homolog of Sox9 (Sox100B), a gene essential for testis formation in humans. The msSGPs are specified in both males and females, but are only recruited into the developing testis. In females, these cells are eliminated via programmed cell death dependent on the sex determination regulatory gene doublesex. Our work furthers the hypotheses that a conserved pathway controls gonad sexual dimorphism in diverse species and that sex-specific cell recruitment and programmed cell death are common mechanisms for creating sexual dimorphism.