Functional analysis of transcriptional repressor RP58 in corticogenesis

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RP58, a transcriptional repressor, is expressed strongly in the developing neocortex and plays an essential role for corticogenesis. From the RP58-KO mice analysis, it is suggested that RP58 is important for neuronal differentiation, survival and migration. In the present study, in order to reveal the molecular mechanism for corticogenesis, RP58 downstream effecter genes and detailed migration defects have been analyzed. As a result, proneural bHLH factor, Ngn2 has been identified as RP58 target gene. Ngn2 activates RP58 transcription first, then induced RP58 represses Ngn2 transcription. This negative feedback mechanism between Ngn2 and RP58 allows transient expression of Ngn2. Using in utero electroporation, it was revealed that RP58 deficient cells can not convert from multipolar to bipolar and enter to locomotion mode in the cortical plate.