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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 06, 2024 |
| Title |
A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis [Set1.Sc-ATAC-Seq retina E14.5 WT retina] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
During retinogenesis, the proneural bHLH transcription factor 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 nonsyndromic congenital retinal nonattachment (NCRNA) disorder, characterized by optic nerve atrophy and complete blindness. Here we functionally interrogate the significance of the Atoh7 enhancer landscape to retinogenesis. We demonstrate that deletion of the enhancer structure upstream of Atoh7 in mice leads to RGC deficiency, optic nerve hypoplasia and blood vascular abnormalities, phenocopying inactivation of Atoh7 and recapitulating key features of NCRNA. We further provide evidence that the loss of the Atoh7 remote enhancer impacts ipsilaterally-projecting RGCs and disrupts proper axonal projections to the brain targets. Transcriptionally, deletion of the Atoh7 remote enhancer is associated with dysregulation of axonogenesis genes, including the derepression of the axon repulsive cue Robo3 which is normally epigenetically silenced in the developing retina. Our data provide novel insights into how Atoh7 enhancer elements function to promote RGC development and optic nerve formation and uncover a key role of Atoh7 in the transcriptional control of axon guidance molecules possibly via epigenetic mechanisms.
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| Overall design |
Sc-ATAC-Seq retina E14.5 WT retina: Two replicates of E14.5 WT retina were dissociated and processed for sc-ATAC-Seq analysis according to 10X genomics protocol.
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| Contributor(s) |
Mehta K, Daghsni M, Bian F, Xu Z, Davis E, Naidich A, Wang B, Pi S, Chen W, Kostka D, Liu S, Gross JM, Kuwajima T, Aldiri I |
| Citation(s) |
38823017 |
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| Submission date |
Oct 17, 2023 |
| Last update date |
Sep 11, 2024 |
| Contact name |
Shuchang Liu |
| E-mail(s) |
shl96@pitt.edu
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| Organization name |
University of Pittsburgh
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| Street address |
203 Lothrop Street
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15261 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE245549 |
A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis |
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| Relations |
| BioProject |
PRJNA1028959 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE245538_RAW.tar |
10.8 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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