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Series GSE245540 Query DataSets for GSE245540
Status Public on Jun 06, 2024
Title A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis [Set2.Bulk RNA-Seq retina E14.5 WT and Atoh7 Large Enhancer KO]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
 
Overall design Bulk RNA-Seq retina E14.5 WT and Atoh7 Large Enhancer KO: four independent replicates from WT or Atoh7 TEN KO retinae at E14.5 were processed for RNA extraction and submitted for RNA-Seq
 
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
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Submission date Oct 17, 2023
Last update date Jun 07, 2024
Contact name Shuchang Liu
E-mail(s) shl96@pitt.edu
Organization name University of Pittsburgh
Department Pathology
Street address 203 Lothrop Street
City Pittsburgh
State/province PA
ZIP/Postal code 15261
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7844751 WT rep1 (Set2)
GSM7844752 WT rep2 (Set2)
GSM7844753 WT rep3 (Set2)
This SubSeries is part of SuperSeries:
GSE245549 A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis
Relations
BioProject PRJNA1028970

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Supplementary file Size Download File type/resource
GSE245540_RAW.tar 1.4 Mb (http)(custom) TAR (of TAB)
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Raw data are available in SRA

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