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Cell Rep ; 35(12): 109269, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34161768

RESUMO

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.


Assuntos
Córtex Cerebral/citologia , Proteínas de Ligação a DNA/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Transcrição Gênica , Alelos , Animais , Diferenciação Celular/genética , Fenômenos Eletrofisiológicos , Regulação da Expressão Gênica , Camundongos Knockout , Mitose/genética , Neurônios/citologia , Ligação Proteica , Proteínas Repressoras/metabolismo
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