Grants and Contracts Details
Description
The retinal neurons arise from a common pool of progenitor cells that are regulated by a
complex set of genes that precisely give rise to all retinal neurons. Any disruption in this
developmental mechanism leads to congenital retinal disorders. Of particular interest to us is
the ocular malformations observed in patients with CHARGE syndrome. Common features of
this disorder are coloboma, heart defects, atresia choanae, growth retardation, genital and ear
abnormalities. The syndrome is caused by mutations in the gene CHD7. Although large number
of patients present coloboma, visual impairment is also observed in patients without coloboma
suggesting that chd7 is also involved in mechanisms during retinal development. Loss of CHD7
leads to reduced number of cone photoreceptors and truncated photoreceptor outer segments.
Our lab has shown that CHD7 is broadly expressed in the retinal progenitors at 24 hpf and
retains strong expression in the ganglion cell layer, inner nuclear layer, and photoreceptors by
the end of progenitor differentiation into retinal neurons. Morpholino experiments in chd7 show a
reduced number of ganglion cells in the morphants. However, the molecular mechanisms and
function of chd7 during retinal development has not been rigorously investigated. In this
proposal, I aim to investigate the early roles of chd7 during retinal ganglion and photoreceptor
cell development utilizing maternal zygotic chd7 mutants in zebrafish which show phenotypes
observed in CHRAGE syndrome. I propose to perform scRNA-seq analysis at various early time
points and utilize a novel CUT&RUN technique established in zebrafish to impinge upon the
temporal dynamics of chd7 binding target regulatory elements. Our lab has established and
generated preliminary data utilizing both techniques. Taken together, our analysis will show
novel insights into how the loss of chd7 impacts retinal progenitor cell differentiation into the
retinal neurons both indirectly and directly including the potential temporal change in chd7
binding activity during retinal development. This analysis could help provide insights into the
development of potential therapeutics for treatment of visual impairment in patients with
CHARGE syndrome.
Status | Finished |
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Effective start/end date | 7/1/23 → 10/16/24 |
Funding
- Knights Templar Eye Foundation Inc: $90,000.00
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