A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis.
Cell Rep
; 43(6): 114291, 2024 Jun 25.
Article
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| MEDLINE
| ID: mdl-38823017
ABSTRACT
Atoh7 is transiently expressed in retinal progenitor cells (RPCs) and is required for retinal ganglion cell (RGC) differentiation. In humans, a deletion in a distal non-coding regulatory region upstream of ATOH7 is associated with optic nerve atrophy and blindness. Here, we functionally interrogate the significance of the Atoh7 regulatory landscape to retinogenesis in mice. Deletion of the Atoh7 enhancer structure leads to RGC deficiency, optic nerve hypoplasia, and retinal blood vascular abnormalities, phenocopying inactivation of Atoh7. Further, loss of the Atoh7 remote enhancer impacts ipsilaterally projecting RGCs and disrupts proper axonal projections to the visual thalamus. Deletion of the Atoh7 remote enhancer is also associated with the dysregulation of axonogenesis genes, including the derepression of the axon repulsive cue Robo3. Our data provide insights into how Atoh7 enhancer elements function to promote RGC development and optic nerve formation and highlight a key role of Atoh7 in the transcriptional control of axon guidance molecules.
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Base de datos:
MEDLINE
Asunto principal:
Células Ganglionares de la Retina
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Axones
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Elementos de Facilitación Genéticos
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article