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Publication : Transcription factors Bcl11a and Bcl11b are required for the production and differentiation of cortical projection neurons.

First Author  Du H Year  2022
Journal  Cereb Cortex Volume  32
Issue  17 Pages  3611-3632
PubMed ID  34963132 Mgi Jnum  J:328712
Mgi Id  MGI:7339087 Doi  10.1093/cercor/bhab437
Citation  Du H, et al. (2022) Transcription factors Bcl11a and Bcl11b are required for the production and differentiation of cortical projection neurons. Cereb Cortex 32(17):3611-3632
abstractText  The generation and differentiation of cortical projection neurons are extensively regulated by interactive programs of transcriptional factors. Here, we report the cooperative functions of transcription factors Bcl11a and Bcl11b in regulating the development of cortical projection neurons. Among the cells derived from the cortical neural stem cells, Bcl11a is expressed in the progenitors and the projection neurons, while Bcl11b expression is restricted to the projection neurons. Using conditional knockout mice, we show that deficiency of Bcl11a leads to reduced proliferation and precocious differentiation of cortical progenitor cells, which is exacerbated when Bcl11b is simultaneously deleted. Besides defective neuronal production, the differentiation of cortical projection neurons is blocked in the absence of both Bcl11a and Bcl11b: Expression of both pan-cortical and subtype-specific genes is reduced or absent; axonal projections to the thalamus, hindbrain, spinal cord, and contralateral cortical hemisphere are reduced or absent. Furthermore, neurogenesis-to-gliogenesis switch is accelerated in the Bcl11a-CKO and Bcl11a/b-DCKO mice. Bcl11a likely regulates neurogenesis through repressing the Nr2f1 expression. These results demonstrate that Bcl11a and Bcl11b jointly play critical roles in the generation and differentiation of cortical projection neurons and in controlling the timing of neurogenesis-to-gliogenesis switch.
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