Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity
- Brandeis University, United States
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- National Institutes of Health, NIDDK, United States
Abstract
Retinoic Acid-Related Orphan Receptor Beta (RORβ) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is largely unknown. We find RORβ is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age in wildtype mice. Loss of RORβ delays excitatory input and disrupts gene expression and chromatin accessibility, with down-regulation of L4 and up-regulation of L5 genes, suggesting a disruption in cellular specification. Expression and binding site accessibility change for many other TFs, including closure of neurodevelopmental TF binding sites and increased expression and binding capacity of activity-regulated TFs. Lastly, a putative target of RORβ, Thsd7a, is down-regulated without RORβ, and Thsd7a knock-out alone disrupts TCA organization in adult barrels.
Data availability
Raw and processed RNA-seq and ATAC-seq files are available at GEO accession GSE138001.
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Cortical RORb is required for layer 4 transcriptional identity and barrel integrityNCBI Gene Expression Omnibus, GSE138001.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (NS109916)
- Erin A Clark
- Michael Rutlin
- Lucia Capano
- Samuel Aviles
- Jordan R Saadon
- Praveen Taneja
- Qiyu Zhang
- James B Bullis
- Timothy Lauer
- Emma Myers
- Anton Schulmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were conducted in accordance with the requirements ofthe Institutional Animal Care and Use Committees at Brandeis University (protocol #17001).
Reviewing Editor
- Anne E West, Duke University School of Medicine, United States
Publication history
- Received: October 2, 2019
- Accepted: August 26, 2020
- Accepted Manuscript published: August 27, 2020 (version 1)
- Version of Record published: September 15, 2020 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity
eLife 9:e52370.
https://doi.org/10.7554/eLife.52370
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