Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity.

Autor:	Clark EA; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Rutlin M; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Capano LS; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Aviles S; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Saadon JR; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Taneja P; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Zhang Q; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Bullis JB; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Lauer T; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Myers E; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States., Schulmann A; Janelia Research Campus, Ashburn, United States., Forrest D; Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK, Bethesda, United States., Nelson SB; Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Aug 27; Vol. 9. Date of Electronic Publication: 2020 Aug 27.
DOI:	10.7554/eLife.52370
Abstrakt:	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. Competing Interests: EC, MR, LC, SA, JS, PT, QZ, JB, TL, EM, AS, DF No competing interests declared, SN Reviewing editor, eLife
Databáze:	MEDLINE
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