The role of E2F1 as downstream target for Rb in cortical development

Abstract

Cell cycle regulation is believed to be crucial to nervous system development. In this study, we investigated whether Rb plays a role in the expression of guidance molecules involved in neuronal migration. We found an ectopic expression of robo2 gene, and an increase in the expression of neogenin gene in the developing cortex in conditional Rb knockout mice, suggesting an involvement for Rb in the expression of these genes. We also investigated whether deregulated activity of E2F1 is involved in the defects observed in Rb mutant mice. Using mice with compound null mutations for Rb and E2F1, we found that ectopic proliferation was rescued, and the aberrant laminar patterning in the cortex was restored, while there was a partial rescue in the survival of Cajal-Retzius neurons. Tangential migration of GABA-ergic interneurons, however, was not rescued. Thus, we have demonstrated that E2F1 is involved in Rb mediated ectopic mitoses, cortical laminar patterning, and partially, for the requirement of Rb in the survival of Cajal-Retzius neurons.