Deciphering the Role of SOX2 During Retinal Development

Kimiasadat Golestaneh, BS - Final Dissertation Defense - HUGEN PhD Candidate Department of Human Genetics Doctoral Candidate, Kimiasadat Golestaneh, BS, will defend the following dissertation on “Deciphering the Role of SOX2 During Retinal Development” COMMITTEE CHAIR: Issam Al Diri, PhD Committee Members: F. Yesim Demirci, MDSusana da Silva, PhDBeth L. Roman, PhD ABSTRACT: Retinogenesis requires precise synchronization of progenitor cell competence, spatial patterning, and cell fate specification. Retinal progenitor cells give rise to all retinal cell types in a highly ordered spatiotemporal manner. However, little is known about the gene regulatory mechanisms that maintain progenitor competence within retinogenesis. SOX2 is a key transcription factor expressed in retinal progenitor cells, a subset of amacrine cells, and Müller glia, and it is essential for neural competence. Mutations in SOX2 are associated with human eye developmental abnormalities, including microphthalmia and anophthalmia, underscoring its significance in eye development. However, the mechanisms by which SOX2 regulates retinal progenitor identity, patterning, and differentiation remain poorly defined. I investigate the role of SOX2 during retinal development, focusing on how SOX2 regulates retinal progenitor cell identity, spatial tissue organization, and the transition from progenitor states to differentiated retinal cell types. This work investigates the effect of Sox2 loss in the developing retina and identifies regulatory changes associated with neural competence, spatial identity, and retinal cell fate specification by using genetic, molecular, transcriptomic, and chromatin accessibility approaches. The findings show that SOX2 is required to sustain retinal progenitor cell identity and to support gene regulatory networks essential for retinal development and patterning. Loss of Sox2 disrupts progenitor identity by shifting the bal