Fat1 regulates astrocyte maturation and angiogenesis in the retina

Abstract

Angiogenesis is a stepwise process leading to blood vessel formation. In the vertebrate retina, endothelial cells are guided by astrocytes migrating along the inner surface, and the two processes are coupled by a tightly regulated cross-talk between the two cell types. Here, we investigated how the FAT1 Cadherin, a regulator of tissue morphogenesis governing tissue cross-talks, influences retinal vascular development. Through late-onset inactivation in the neural lineage in mice, we bypassed an early contribution of Fat1 to eye development, and assessed its requirement for postnatal retina angiogenesis. We found that neural Fat1 expression, by controlling the polarity of astrocyte progenitor migration, regulates astrocyte maturation. By interfering with astrocyte migration and maturation, neural Fat1 deletion deregulates the astrocyte/endothelial cell coupling, and delays retinal angiogenesis. Mice with neural-Fat1 ablation exhibit persistent abnormalities of the retinal vascular architecture, such as an increased vascular density in deep layers. Altogether, this study identifies Fat1 as a regulator of neurovascular communication, essential for retinal vascular development and integrity.angiogenic factors produced by neural cells is key to orchestrate astrocyte/endothelial cell 52 coupling, hence influencing the timing and dynamics of angiogenesis. 53

N-cadherin suppression enhances inner limiting membrane permeability for intravitreal cellular transplantation

“…FAT1 (FAT Atypical Cadherin 1) has been reported to modulate retinal vascular development and integrity. Its neural ablation affects ILM integrity in the postnatal mouse retina, possibly due to compromised adhesion between astrocytes and MG 43 . MG express a wide variety of CAMs, which re ects the diverse interactions and supporting roles that they have with other retinal cells.…”