title: Mutually repressive interaction between Brn1/2 and Rorb contributes to the establishment of neocortical layer 2/3 and layer 4.
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.
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan kazunori@keio.jp Koji.Oishi@crick.ac.uk.
authors.forename: Koji
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Aramaki
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan kazunori@keio.jp Koji.Oishi@crick.ac.uk.
authors.forename: Kazunori
authors.identifier: http://orcid.org/0000-0003-1864-9425
authors.initials: K
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2 / Q000235:genetics / Q000378:metabolism*; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D009419:Nerve Tissue Proteins; D057095:Nuclear Receptor Subfamily 1, Group F, Member 2; D050809:POU Domain Factors; C539741:Rorb protein, mouse; C074065:Pou3f3 protein, mouse; C074066:Pou3f2 protein, mouse
keywords: cell fate; cerebral cortex; layer formation; transcription factor