Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):167-72. doi: 10.1073/pnas.1010299108. Epub 2010 Dec 20.
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.
新的睾丸索组织在胎儿性腺中的起始过程知之甚少。内皮细胞迁移到 XY 性腺中启动睾丸形态发生。然而，调节性腺血管生成的信号以及血管影响组织形态发生的机制尚不清楚。在这里，我们表明 Vegf 信号对于性腺血管生成和索状结构的形成是必需的。我们确定间质细胞表达 Vegfa，并通过增殖对内皮细胞迁移做出反应。在没有脉管系统的情况下，对整个器官的四维成像显示，间质细胞的增殖减少，并且阻止了将性腺分隔成形成索状结构的楔形结构的形成。抑制血管成熟也会降低增殖。然而，添加 PDGF-BB 可挽救间充质细胞的增殖。这些结果表明了一条整合血管发育和睾丸索状结构形成的途径，并提出了一个模型，其中未分化的间充质募集血管，响应增殖，并在发育器官的形态发生和模式形成中发挥主要功能。
