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 indicated that the 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 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 acceleration of the migration of immature ganglion cells and repressing apoptosis. Our study reveals an unreported role for 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.

Zebrafish Kit ligands cooperate with erythropoietin to promote erythroid cell expansion

“…13,15 In mammals, KIT signaling is associated with erythropoiesis and myelopoiesis, 16 as well as with neurogenesis and pigmentation. 13,[17][18][19] Interestingly, 2 forms of KITLG occur in vivo: transmembrane (TM), which is important for the regulation of stem cells in their niches, and soluble, which affects more distant tissues. 13,20 Binding of KITLG to its receptor KIT, a member of the receptor tyrosine kinase type-III family, leads to its autophosphorylation, further triggering various signaling cascades, including the phosphatidylinositol 3-kinase, MAPK, SRC, and JAK pathways.…”

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids

“…The near physiological 3D ROs present a stratified structure, most major retinal cell types, complex interactions, and light-responsive function. 35–37 However, the retinal components in any organoids cannot be exactly recapitulated in the native retina to size, structure, and function. In addition, the generation and differentiation of ROs are not well controlled due to a lack of knowledge about the actual microenvironment.…”

Ethanol Causes Cell Death and Neuronal Differentiation Defect During Initial Neurogenesis of the Neural Retina by Disrupting Calcium Signaling in Human Retinal Organoids

“…The induction of hROs was performed in accordance with our previous study [49]. Brie y, hESCs were dissociated and re-aggregated (9,000 cells per well) using low-cell adhesion 96-well plates (Sumitomo Bakelite) in growth factor-free chemically de ned medium (gfCDM) which contained 45% Iscove's modi ed Dulbecco's medium (IMDM, Gibco), 45% Hams F12 (F12, Gibco), Glutamax, 1% chemically de ned lipid concentrate (Gibco), 10% Knockout Serum Replacement (KSR) (Gibco), monothioglycerol (450 µM, Sigma), 100 U/mL penicillin, and 100 µg/mL streptomycin (Gibco).…”