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Development ; 148(16)2021 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-34351428

RESUMEN

Neocortical progenitor cells generate subtypes of excitatory projection neurons in sequential order followed by the generation of astrocytes. The transcription factor zinc finger and BTB domain-containing protein 20 (ZBTB20) has been implicated in regulation of cell specification during neocortical development. Here, we show that ZBTB20 instructs the generation of a subset of callosal projections neurons in cortical layers II/III in mouse. Conditional deletion of Zbtb20 in cortical progenitors, and to a lesser degree in differentiating neurons, leads to an increase in the number of layer IV neurons at the expense of layer II/III neurons. Astrogliogenesis is also affected in the mutants with an increase in the number of a specific subset of astrocytes expressing GFAP. Astrogliogenesis is more severely disrupted by a ZBTB20 protein containing dominant mutations linked to Primrose syndrome, suggesting that ZBTB20 acts in concert with other ZBTB proteins that were also affected by the dominant-negative protein to instruct astrogliogenesis. Overall, our data suggest that ZBTB20 acts both in progenitors and in postmitotic cells to regulate cell fate specification in the mammalian neocortex.


Asunto(s)
Astrocitos/metabolismo , Neocórtex/crecimiento & desarrollo , Neurogénesis/genética , Neuronas/metabolismo , Factores de Transcripción/metabolismo , Anomalías Múltiples/genética , Animales , Calcinosis/genética , Enfermedades del Oído/genética , Femenino , Técnicas de Inactivación de Genes , Discapacidad Intelectual/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Atrofia Muscular/genética , Mutación Missense , Neocórtex/metabolismo , Transducción de Señal/genética , Células Madre/metabolismo , Factores de Transcripción/genética
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