Receptor tyrosine kinase signaling in astrocyte migration and angiogenesis

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PROJECT SUMMARY Retinal astrocytes form the integral part of the neural-glial-vascular network in the retina. They contribute to the establishment of the retinal vasculature, maintenance of the blood-retina barrier and health of retinal ganglion cells. Although several signaling pathways are known to be active in astrocytes, how they are integrated to regulate astrocyte development and physiology is still poorly understood. This project will investigate the role and mechanism of PDGF and FGF signaling, two closely related receptor tyrosine kinase pathways, in astrocyte development. By generating mouse mutants and performing living imaging, we will delineate the PDGF signaling cascade specific to astrocytes and understand how it regulates the migratory behaviors of astrocytes. Furthermore, we will investigate the molecular mechanism of FGF signaling in regulating astrocyte maturation. Lastly, we will test the hypothesis that FGF and PDGF signaling are required for suppression of astrocyte maturation and induction of angiogenesis. Astrocytic malfunction can lead to impaired retinal vascularization, breakdown of the blood-retinal-barrier and reactive gliosis, contributing to a cohort of blinding diseases such as retinopathy of prematurity (ROP), coloboma, and glaucoma. This project is expected to illuminate the mechanism of PDGF and FGF signaling in astrocytes, which will contribute to understanding and treatment of ocular diseases.