PlexinD1 is required for proper patterning of the periocular vascular network and for the establishment of corneal avascularity during avian ocular development.
PlexinD1 is required for proper patterning of the periocular vascular network and for the establishment of corneal avascularity during avian ocular development.
复制标题
DOI：
10.1016/j.ydbio.2016.01.001
复制
发表时间：
2016-03-01
影响因子：
2.7
通讯作者：
Lwigale PY
中科院分区：
文献类型：
--
作者：
Kwiatkowski SC;Ojeda AF;Lwigale PY
前眼由被致密的眼周血管网包围的无血管角膜组成，因此用作血管生成的极好模型。虽然通过丛蛋白D1的信号转导是胚胎发育过程中各种血管图案形成事件的基础，但其在眼周血管网络形成过程中的作用尚未确定。我们最近的研究表明，PlexinD1 mRNA表达的眼周成血管细胞和血管在眼血管发生的模式，这表明其参与与Sema3配体，同时在前眼表达。在这项研究中，我们使用在体内敲除实验，以确定在血管图案的发育中的鸟类胚胎的前眼丛蛋白D1的作用。前眼中PlexinD1的敲除导致假定虹膜中的血管网络的图案错误，这伴随着血管完整性的丧失和前房中的大量膨胀。我们还观察到在PlexinD1敲除眼中角膜的异位血管形成，这与对照组中角膜缘血管的形成一致。最后，我们表明，Sema3E和Sema3C转录表达的眼组织是缺乏血管。这些结果表明，丛蛋白D1在虹膜和利姆布斯的血管形成过程中起着关键作用，并且对于发育过程中角膜无血管性的建立至关重要。我们的结论是，丛蛋白D1参与血管反应的抗血管生成Sema3信号，指导形成的虹膜和角膜缘血管抑制VEGF信号。
The anterior eye is comprised of an avascular cornea surrounded by a dense periocular vascular network and therefore serves as an excellent model for angiogenesis. Although signaling through PlexinD1 underlies various vascular patterning events during embryonic development, its role during the formation of the periocular vascular network is yet to be determined. Our recent study showed that PlexinD1 mRNA is expressed by periocular angioblasts and blood vessels during ocular vasculogenesis in patterns that suggest its involvement with Sema3 ligands that are concurrently expressed in the anterior eye. In this study, we used in vivo knockdown experiments to determine the role of PlexinD1 during vascular patterning in the anterior eye of the developing avian embryos. Knockdown of PlexinD1 in the anterior eye caused mispatterning of the vascular network in the presumptive iris, which was accompanied by lose of vascular integrity and profuse hemorrhaging in the anterior chamber. We also observed ectopic vascularization of the cornea in PlexinD1 knockdown eyes, which coincided with the formation of the limbal vasculature in controls. Finally we show that Sema3E and Sema3C transcripts are expressed in ocular tissue that is devoid of vasculature. These results indicate that PlexinD1 plays a critical role during vascular patterning in the iris and limbus, and is essential for the establishment of corneal avascularity during development. We conclude that PlexinD1 is involved in vascular response to antiangiogenic Sema3 signaling that guides the formation of the iris and limbal blood vessels by inhibiting VEGF signaling.