Regulation of brain development and brain function by the transcriptional repressor RP58

•In the developing cortex, Rp58 (also known Znf238, Zfp238, Zbtb18), a sequence-specific transcriptional repressor, is expressed in glutamatergic projection neurons and progenitor cells. Rp58-deficient mice have a higher progenitor cell number. RP58 represses all four Id genes (Id1-Id4), which regulate cell-cycle exit in the developing cerebral cortex, and RP58 represses Ngn2 and Rnd2, which regulate the multipolar-to-bipolar transition during neuronal migration independent of its role in cell-cycle exit (Okado et al., 2009; Hirai et al., 2012; Ohtaka-Maruyama et al., 2013). The mechanisms regulating the formation of the cerebral cortex have been well studied. In the developing cortex, (also known Znf238, Zfp238, and Zbtb18), which encodes a sequence-specific transcriptional repressor, is expressed in glutamatergic projection neurons and progenitor cells. Targeted deletion of Rp58 leads to dysplasia of the neocortex and hippocampus, a reduction in the number of mature cortical neurons, and defects in laminar organization due to abnormal neuronal migration within the cortical plate. During late embryogenesis, Rp58-deficient mice have larger numbers of progenitor cells due to a delay in cell cycle exit. RP58 represses all four Id genes (Id1–Id4), which regulate cell cycle exit in the developing cerebral cortex, and is essential for transcriptional repression of Ngn2 and Rnd2, which regulate the multipolar-to-bipolar transition during neuronal migration independently of its role in cell cycle exit.