Cell fate decisions, transcription factors and signaling during early retinal development.
Cell fate decisions, transcription factors and signaling during early retinal development.
复制标题
细胞命运的决策，转录因子和信号传导早期发育。
DOI：
10.1016/j.preteyeres.2022.101093
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发表时间：
2022-11
影响因子：
17.8
通讯作者：
Cvekl, Ales
中科院分区：
文献类型：
--
作者：
Diacou, Raven;Nandigrami, Prithviraj;Fiser, Andras;Liu, Wei;Ashery-Padan, Ruth;Cvekl, Ales
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-腹模式开始，导致视野的形成。在前神经板处眼区的对称分离之后是两个对称的外翻，以产生一对视泡。接着，视泡与表面外胚层衍生的透镜基板相互内陷产生双层视杯。视杯的内层和外层分别发育成神经视网膜和视网膜色素上皮（RPE）。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，模拟体内视网膜分化的主要步骤。本文综述了眼早期发育的最新进展，重点介绍了眼野、视泡和早期视杯的形成。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，以揭示早期眼睛发育的一系列细胞机制。信号转导通路和谱系特异性DNA结合转录因子的功能进行解剖，以解释细胞特异性的调节机制，在早期眼睛发育过程中的细胞命运的决定。本文详细讨论了眼早期发育所需的同源域转录因子Otx 2、Pax 6、Lhx 2、Six 3和Six 6的功能。对早期眼发育机制的全面了解为深入了解发育性眼异常（如视杯缺损）的分子和细胞基础提供了依据。最后，使用干细胞衍生的视网膜类器官对人类发育和遗传性视网膜疾病进行建模，为发现视网膜疾病的新疗法提供了机会。
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.