Abstract
Transcription factors regulate multiple processes during brain development and in the adult brain, from brain patterning to differentiation and maturation of highly specialized neurons as well as establishing and maintaining the functional neuronal connectivity. The members of the zinc-finger transcription factor family Bcl11 are mainly expressed in the hematopoietic and central nervous systems regulating the expression of numerous genes involved in a wide range of pathways. In the brain Bcl11 proteins are required to regulate progenitor cell proliferation as well as differentiation, migration, and functional integration of neural cells. Mutations of the human Bcl11 genes lead to anomalies in multiple systems including neurodevelopmental impairments like intellectual disabilities and autism spectrum disorders.
Highlights
Transcription factors regulate multiple processes during brain development and in the adult brain, from brain patterning to differentiation and maturation of highly specialized neurons as well as establishing and maintaining the functional neuronal connectivity
Emerging evidence demonstrates that Bcl11 proteins execute important functions during central nervous system development and in adult neurogenesis (Arlotta et al, 2005, 2008; Kuo et al, 2009, 2010a,b; John et al, 2012; Simon et al, 2012, 2016; Canovas et al, 2015; Wiegreffe et al, 2015; Greig et al, 2016; Woodworth et al, 2016; De Bruyckere et al, 2018)
The binding of Bcl11 proteins was more efficient when both motifs were present as was shown for desmoplakin (Dsp), a direct Bcl11b target gene activated during dentate gyrus development (Simon et al, 2012), and Semaphorin 3c (Sema3c), directly regulated by Bcl11a (Wiegreffe et al, 2015)
Summary
Transcription factors regulate multiple processes during brain development and in the adult brain, from brain patterning to differentiation and maturation of highly specialized neurons as well as establishing and maintaining the functional neuronal connectivity. Emerging evidence demonstrates that Bcl11 proteins execute important functions during central nervous system development and in adult neurogenesis (Arlotta et al, 2005, 2008; Kuo et al, 2009, 2010a,b; John et al, 2012; Simon et al, 2012, 2016; Canovas et al, 2015; Wiegreffe et al, 2015; Greig et al, 2016; Woodworth et al, 2016; De Bruyckere et al, 2018). Possible functions could include self-regulation of Bcl11 protein activity by assembling of diverse dimers and protein complexes comprised of specific isoforms or factors like the NuRD complex allowing or preventing nuclear translocation and/or DNA binding.
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