[R01] Wiring and rewiring of the chromatin landscape during retinogenesis
Ente: National Eye Institute
Scadenza: 2029-03-31
Importo max: 413.741 EUR
Paese: US
Descrizione
SUMMARY: The proper execution of transcriptional programs in retinal progenitor cells is
extremely critical for retinal formation as dysregulation of this process leads to severely
compromised retinogenesis and the development of ocular disorders, including anophthalmia or
microphthalmia. The wiring and rewiring of chromatin landscape constitutes an essential
mechanism to precise spatial and temporal regulation of gene expression during retinal
differentiation, yet our understanding to this process remains inadequate. Our goal is to utilize
state-of-the-art genomic technologies to provide a deep understanding to the genetic and
epigenetic circuits that underlie retinal transcription programs and how perturbations in the retinal
core regulatory networks lead to congenital syndromes. In the first aim of this proposal, we will
use mouse models to dissect the molecular, cellular, and genomic effects of genetic mutations on
retinal development. In aim 2, we will elucidate how the chromatin landscape is wired by
transcription factors in retinal progenitor cells. In aim 3, we will explore how coordination among
components of the core regulatory network drive retinogenesis epigenetically and
transcriptionally. When completed, the results of this proposal will bridge a gap in our
understanding to the chromatin-based regulatory mechanism underlying retinal genesis, a
necessary knowledge to enhance strategies to diagnose, treat or prevent the devastating
consequences of congenital vision deficiency.
Istituzione: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
PI: Issam Al Diri
Progetto: 5R01EY035619-03
Settori: National Eye Institute
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