Transcriptional regulation of the retinoblastoma family member p107 by Dlx homeobox genes during central nervous system development

Abstract

Objective: The absence of Dlx1/Dlx2 results in defects in neural differentiation and migration in the developing forebrain and retina. To further understand genetic regulation of neural differentiation and migration by Dlx genes, we examined transcriptional regulation of p107. Results: DLX2 occupies the p107 promoter in situ in the developing forebrain and retina and binds directly to sequences for the p107 promoter in vitro. In the absence of Dlx1/Dlx2, we observe reduced p107 expression. DLX2 binding to the p107 promoter results in significant activation of luciferase reporter gene expression in vitro. Conclusions: DLX2 binds to the p107 promoter in situ and in vitro, resulting in the activation of p107 expression in both the developing forebrain and retina. These findings contribute to our knowledge of genetic regulation of neurogenesis by Dlx homeobox genes and may contribute to identification of novel targets for disorders of neuronal differentiation and migration.