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.
-
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).
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.
Metrics
-
- 2,773
- views
-
- 302
- downloads
-
- 39
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 39
- citations for umbrella DOI https://doi.org/10.7554/eLife.52370
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity
eLife 9:e52370.
https://doi.org/10.7554/eLife.52370
