4.6 Review

Retinogenesis of the Human Fetal Retina: An Apical Polarity Perspective

期刊

GENES
卷 10, 期 12, 页码 -

出版社

MDPI
DOI: 10.3390/genes10120987

关键词

apical polarity; crumbs complex; fetal retina; PAR complex; retinal organoids; retinogenesis; gene augmentation; adeno-associated virus (AAV); Leber congenital amaurosis

资金

  1. Foundation Fighting Blindness [TA-GT-0715-0665-LUMC]
  2. Netherlands Organisation for Health Research and Development [43200004]
  3. Curing Retinal Blindness Foundation
  4. Stichting Retina Nederland Fonds
  5. Landelijke St. Blinden en Slechtzienden
  6. Rotterdamse Stichting, Blindenbelangen
  7. St. Blindenhulp
  8. St. Blinden- Penning
  9. MaculaFonds

向作者/读者索取更多资源

The Crumbs complex has prominent roles in the control of apical cell polarity, in the coupling of cell density sensing to downstream cell signaling pathways, and in regulating junctional structures and cell adhesion. The Crumbs complex acts as a conductor orchestrating multiple downstream signaling pathways in epithelial and neuronal tissue development. These pathways lead to the regulation of cell size, cell fate, cell self-renewal, proliferation, differentiation, migration, mitosis, and apoptosis. In retinogenesis, these are all pivotal processes with important roles for the Crumbs complex to maintain proper spatiotemporal cell processes. Loss of Crumbs function in the retina results in loss of the stratified appearance resulting in retinal degeneration and loss of visual function. In this review, we begin by discussing the physiology of vision. We continue by outlining the processes of retinogenesis and how well this is recapitulated between the human fetal retina and human embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal organoids. Additionally, we discuss the functionality of in utero and preterm human fetal retina and the current level of functionality as detected in human stem cell-derived organoids. We discuss the roles of apical-basal cell polarity in retinogenesis with a focus on Leber congenital amaurosis which leads to blindness shortly after birth. Finally, we discuss Crumbs homolog (CRB)-based gene augmentation.

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