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Fat1 regulates astrocyte maturation and angiogenesis in the retina

View ORCID ProfileFrançoise Helmbacher
doi: https://doi.org/10.1101/2020.04.23.057141
Françoise Helmbacher
1Aix Marseille Univ, CNRS, IBDM UMR 7288, Parc Scientifique de Luminy, Case 907, 13288 Marseille, France
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  • ORCID record for Françoise Helmbacher
  • For correspondence: francoise.helmbacher@univ-amu.fr
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 24, 2020.
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Fat1 regulates astrocyte maturation and angiogenesis in the retina
Françoise Helmbacher
bioRxiv 2020.04.23.057141; doi: https://doi.org/10.1101/2020.04.23.057141
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Fat1 regulates astrocyte maturation and angiogenesis in the retina
Françoise Helmbacher
bioRxiv 2020.04.23.057141; doi: https://doi.org/10.1101/2020.04.23.057141

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