Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity
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 transcripti...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-08-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/52370 |
| _version_ | 1827804240578347008 |
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| author | Erin A Clark Michael Rutlin Lucia S Capano Samuel Aviles Jordan R Saadon Praveen Taneja Qiyu Zhang James B Bullis Timothy Lauer Emma Myers Anton Schulmann Douglas Forrest Sacha B Nelson |
| author_facet | Erin A Clark Michael Rutlin Lucia S Capano Samuel Aviles Jordan R Saadon Praveen Taneja Qiyu Zhang James B Bullis Timothy Lauer Emma Myers Anton Schulmann Douglas Forrest Sacha B Nelson |
| author_sort | Erin A Clark |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T21:08:03Z |
| format | Article |
| id | doaj.art-a143c7c6917545f59744ceeea1ce5c98 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T21:08:03Z |
| publishDate | 2020-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a143c7c6917545f59744ceeea1ce5c982023-09-29T10:42:42ZengeLife Sciences Publications LtdeLife2050-084X2020-08-01910.7554/eLife.52370Cortical RORβ is required for layer 4 transcriptional identity and barrel integrityErin A Clark0https://orcid.org/0000-0002-4013-325XMichael Rutlin1Lucia S Capano2https://orcid.org/0000-0003-3470-9360Samuel Aviles3Jordan R Saadon4Praveen Taneja5Qiyu Zhang6https://orcid.org/0000-0002-7141-4046James B Bullis7Timothy Lauer8Emma Myers9Anton Schulmann10Douglas Forrest11Sacha B Nelson12https://orcid.org/0000-0002-0108-8599Department of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesJanelia Research Campus, Ashburn, United StatesLaboratory of Endocrinology and Receptor Biology, National Institutes of Health, NIDDK, Bethesda, United StatesDepartment of Biology and Program in Neuroscience, Brandeis University, Waltham, United StatesRetinoic 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.https://elifesciences.org/articles/52370neocortexbarrel cortexlayer 4thalamocorticalsomatosensory |
| spellingShingle | Erin A Clark Michael Rutlin Lucia S Capano Samuel Aviles Jordan R Saadon Praveen Taneja Qiyu Zhang James B Bullis Timothy Lauer Emma Myers Anton Schulmann Douglas Forrest Sacha B Nelson Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity eLife neocortex barrel cortex layer 4 thalamocortical somatosensory |
| title | Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity |
| title_full | Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity |
| title_fullStr | Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity |
| title_full_unstemmed | Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity |
| title_short | Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity |
| title_sort | cortical rorβ is required for layer 4 transcriptional identity and barrel integrity |
| topic | neocortex barrel cortex layer 4 thalamocortical somatosensory |
| url | https://elifesciences.org/articles/52370 |
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