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Transcriptional repression by FEZF2 restricts alternative identities of cortical projection neurons

Projection neuron subtype identities in the cerebral cortex are established by expressing pan-cortical and subtype-specific effector genes that execute terminal differentiation programs bestowing neurons with a glutamatergic neuron phenotype and subtype-specific morphology, physiology, and axonal pr...

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Detalles Bibliográficos
Autores principales: Tsyporin, Jeremiah, Tastad, David, Ma, Xiaokuang, Nehme, Antoine, Finn, Thomas, Huebner, Liora, Liu, Guoping, Gallardo, Daisy, Makhamreh, Amr, Roberts, Jacqueline M., Katzman, Solomon, Sestan, Nenad, McConnell, Susan K., Yang, Zhengang, Qiu, Shenfeng, Chen, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327856/
https://www.ncbi.nlm.nih.gov/pubmed/34161768
http://dx.doi.org/10.1016/j.celrep.2021.109269
Descripción
Sumario:Projection neuron subtype identities in the cerebral cortex are established by expressing pan-cortical and subtype-specific effector genes that execute terminal differentiation programs bestowing neurons with a glutamatergic neuron phenotype and subtype-specific morphology, physiology, and axonal projections. Whether pan-cortical glutamatergic and subtype-specific characteristics are regulated by the same genes or controlled by distinct programs remains largely unknown. Here, we show that FEZF2 functions as a transcriptional repressor, and it regulates subtype-specific identities of both corticothalamic and subcerebral neurons by selectively repressing expression of genes inappropriate for each neuronal subtype. We report that TLE4, specifically expressed in layer 6 corticothalamic neurons, is recruited by FEZF2 to inhibit layer 5 subcerebral neuronal genes. Together with previous studies, our results indicate that a cortical glutamatergic identity is specified by multiple parallel pathways active in progenitor cells, whereas projection neuron subtype-specific identity is achieved through selectively repressing genes associated with alternate identities in differentiating neurons.