ArticleProceedings of the National Academy of Sciences of the United States of America2016
Mutually repressive interaction between Brn1/2 and Rorb contributes to the establishment of neocortical layer 2/3 and layer 4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 87 citations in OpenAlex.
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- Differential neurogenic patterns underlie the formation of primary and secondary areas in the developing somatosensory cortex.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X.Biology open · 2025Article
- Cortical somatostatin long-range projection neurons and interneurons exhibit divergent developmental trajectories.Neuron · 2024Article
- Selective Vulnerability to Neurodegenerative Disease: Insights from Cell Type-Specific Translatome Studies.Biology · 2024Review
- Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development.Nature communications · 2023Article
- An allelic series of spontaneous Rorb mutant mice exhibit a gait phenotype, changes in retina morphology and behavior, and gene expression signatures associated with the unfolded protein response.G3 (Bethesda, Md.) · 2023Article
- Activation of Sonic Hedgehog Signaling Promotes Differentiation of Cortical Layer 4 Neurons via Regulation of Their Cell Positioning.Journal of developmental biology · 2022Article
- Comparing the development of cortex-wide gene expression patterns between two species in a common reference frame.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Although several molecules have been shown to play important roles in subtype specification of neocortical neurons, the entire mechanism involved in the specification, in particular, of upper cortical plate (UCP) neurons still remains unclear. The UCP, which is responsible for intracortical connections in the neocortex, comprises histologically, functionally, and molecularly different layer 2/3 (L2/3) and L4. Here, we report the essential interactions between two types of transcription factors, Rorb (RAR-related orphan receptor beta) and Brn1/2 (Brain-1/Brain-2), for UCP specification. We found that Brn2 expression was detected in all upper layers in the immature UCP, but was subsequently restricted to L2/3, accompanied by up-regulation of Rorb in L4, suggesting demarcation of L2/3 and L4 during cortical maturation. Rorb indeed inhibited Brn2 expression and the expression of other L2/3 characteristics, revealed by ectopic expression and knockdown studies. Moreover, this inhibition occurred through direct binding of Rorb to the Brn2 locus. Conversely, Brn1/2 also inhibited Rorb expression and the expression of several L4 characteristics. Together, these results suggest that a mutually repressive mechanism exists between Brn1/2 and Rorb expression and that the established expression of Brn1/2 and Rorb further specifies those neurons into L2/3 and L4, respectively, during UCP maturation.
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