SCF/SCFR signaling plays an important role in the early morphogenesis and neurogenesis of human embryonic neural retina

Abstract

The stem cell factor receptor (SCFR) has been demonstrated to be expressed in the neural retina of mice, rat, and human for decades. Previous reports indicate that SCFR correlates with glia differentiation of late retinal progenitor cells (RPCs), retinal vasculogenesis, and homeostasis of the blood-retinal barrier. However, the role of SCF/SCFR signaling in the growth and development of the neural retina (NR), especially in the early embryonic stage, remains poorly understood. Here we show that the SCF/SCFR signaling orchestrates invagination of the human embryonic stem cell (hESC)-derived NR via regulation of cell cycle progression, cytoskeleton dynamic, and apical constriction of RPCs in the ciliary marginal zone (CMZ). Furthermore, activation of SCF/SCFR signaling promotes neurogenesis in the central-most NR via accelerating the migration of immature ganglion cells and repressing apoptosis. Our study reveals an unreported role of SCF/SCFR signaling in controlling ciliary marginal cellular behaviors during early morphogenesis and neurogenesis of the human embryonic NR, providing a new potential therapeutic target for human congenital eye diseases such as anophthalmia, microphthalmia, and congenital high myopia.