Role of Chemorepellants during Neural Crest Migration in the Eye

在角膜发育和再生过程中引导细胞迁移的分子信号是 大部分是unl<nown。神经嵴细胞从眼周区域迁移到发育中的眼睛， 角膜基质和内皮。神经嵴发育缺陷与彼得氏综合征有关 异常和Axenfeid-Rieger综合征，而它们的角膜细胞后代参与伤口 导致疤痕形成的愈合过程，cheoKireplicent SemaphorinSA之间的相互作用 （SemaSA）及其受体Neuropllin-1（Npn-1）在整个发育过程中被反复利用，并发挥着重要作用。 在引导细胞迁移和轴突投射中起重要作用。然而，它们在眼睛发育过程中的作用 伤口的愈合也没有被检查过。我们已经证明，透镜衍生的SemaSA调节角膜上皮细胞的生长。 发育过程中的神经支配，这是角膜神经和形成的适当分割所必需的 腹侧神经丛我们还观察到Sema 3A和Npn-1在透镜中表达， 在眼发育早期，Npn-1在眼周神经嵴中表达下调， 神经嵴迁移到退化眼。此外，Npn-1和SemaSA是不同的。 在角膜再生过程中表达。因此，我们假设Sema 3/^Npn-1信号传导是重要的， 用于调节角膜发育过程中眼周神经嵴和角膜细胞的迁移， 再生为了验证这一假设，我们将结合联合收割机经典的胚胎学技术，遗传分析， 分子生物学和视频显微镜检查Npn-1和SemaSA的作用， 在这些事件期间实时地观察波峰迁移。实验将在chicl和小鼠中进行，因为每个 该模型具有独特的实验优势。将制定以下具体目标：1）审查 神经嵴细胞迁移到角膜的体内延时视频显微镜。2)表征和 研究Npn-1和SemaSA在小鼠眼睛发育过程中的作用。3)分析NPN的作用- 1/角膜伤口愈合期间的Sema 3A相互作用。

The molecular signals that guitde cell migration during development and regeneration of the cornea are largely unl<nown. Neural crest cells migrate from the periocular region Into the developing eye and give rise to the cornea stroma and endothelium. Defects In neural crest development are associated wltii Peter's anomaly and Axenfeid-Rieger syndrome, whereas their keratocyte progeny are Involved In the wound healing process that results in scar formation, interactions between the cheoKirepetient SemaphorinSA (SemaSA) and its receptor Neuropllin-1 (Npn-1) are utilized repeatedly throughout development and play a significant role in directing ceil migration and axon projections. However their role during eye development and wound healing has not been examined. We have shown that lens derived SemaSA regulates corneal innervation during development, which is required for the proper partening oif corneal nerves and formation of the ventral plexus. We have also observed that Sema3A and Npn-1 are expressed in the lens and periocular neural crest respectively, early during eye development, but Npn-1 is down-regulated during neural crest migration into the rudimentary eye. Furthermore, Npn-1 and SemaSA are differentially expressed during cornea regeneration. We therefore hypothesize that Sema3/^Npn-1 signaling is important for regulating migration of periocular neural crest and l<eratocytes during cornea development and regeneration. To test this hypothesis, we will combine classical embryological techniques, genetic analysis, molecular biology and video microscopy to examine the role of Npn-1 and SemaSA and visualize neural crest migration in real-time during these events. Experiments will be carried out in chicl< and mouse, as each model offers unique experimental advantages. The following specific aims will be peri'ormed: 1) Examine the migration of neural crest cells Into the cornea by in vivo time-lapse video microscopy. 2) Characterize and examine the role of Npn-1 and SemaSA during mouse eye development. 3) Examine the role of Npn- 1/Sema3A interactions during cornea wound healing.