PDF(Pubmed)
Abstract：
The development of the vertebrate eyes is a complex process starting from anterior-posterior and dorso-ventral patterning of the anterior neural tube, resulting in the formation of the eye field. Symmetrical separation of the eye field at the anterior neural plate is followed by two symmetrical evaginations to generate a pair of optic vesicles. Next, reciprocal invagination of the optic vesicles with surface ectoderm-derived lens placodes generates double-layered optic cups. The inner and outer layers of the optic cups develop into the neural retina and retinal pigment epithelium (RPE), respectively. In vitro produced retinal tissues, called retinal organoids, are formed from human pluripotent stem cells, mimicking major steps of retinal differentiation in vivo. This review article summarizes recent progress in our understanding of early eye development, focusing on the formation the eye field, optic vesicles, and early optic cups. Recent single-cell transcriptomic studies are integrated with classical in vivo genetic and functional studies to uncover a range of cellular mechanisms underlying early eye development. The functions of signal transduction pathways and lineage-specific DNA-binding transcription factors are dissected to explain cell-specific regulatory mechanisms underlying cell fate determination during early eye development. The functions of homeodomain (HD) transcription factors Otx2, Pax6, Lhx2, Six3 and Six6, which are required for early eye development, are discussed in detail. Comprehensive understanding of the mechanisms of early eye development provides insight into the molecular and cellular basis of developmental ocular anomalies, such as optic cup coloboma. Lastly, modeling human development and inherited retinal diseases using stem cell-derived retinal organoids generates opportunities to discover novel therapies for retinal diseases.
摘要：
脊椎动物眼睛的发育是一个复杂的过程，从前神经管的前后和背腹图案开始，导致眼场的形成。前神经板处的眼场对称分离，然后进行两个对称的逃避，以生成一对光学囊泡。接下来,光学囊泡与表面外胚层衍生的晶状体斑相互内陷会产生双层光学杯。视杯的内层和外层发育成神经视网膜和视网膜色素上皮（RPE），分别。体外产生的视网膜组织，称为视网膜类器官，由人类多能干细胞形成，模仿体内视网膜分化的主要步骤。这篇综述文章总结了我们对早期眼睛发育的理解的最新进展，专注于眼场的形成，视神经囊泡，和早期的光学杯。最近的单细胞转录组学研究与经典的体内遗传和功能研究相结合，以揭示早期眼部发育的一系列细胞机制。解剖了信号转导途径和谱系特异性DNA结合转录因子的功能，以解释在早期眼部发育过程中细胞命运决定的细胞特异性调节机制。同源域（HD）转录因子Otx2，Pax6，Lhx2，Six3和Six6的功能，这是早期眼部发育所必需的，详细讨论。对早期眼部发育机制的全面了解可以深入了解眼部发育异常的分子和细胞基础，如视杯结肠瘤。最后,使用干细胞衍生的视网膜类器官模拟人类发育和遗传性视网膜疾病，为发现视网膜疾病的新疗法提供了机会。
