Human antigen R-regulated mRNA metabolism promotes the cell motility of migrating neurons

Abstract

Neocortex development during embryonic stages requires the precise control of mRNA metabolism. Human antigen R (HuR) is a well-studied mRNA binding protein that regulates mRNA metabolism, and it is highly expressed in the neocortex during developmental stages. Deletion of HuR does not impair neural progenitor cell proliferation or differentiation, but it disturbs the laminar structure of the neocortex. We report that HuR was expressed in postmitotic projection neurons during brain development. Specifically, depletion of HuR in these neurons led to a mislocalization of CDP+ neurons in deeper layers of the cortex. Time-lapse microscopy showed that HuR was required for the promotion of cell motility in migrating neurons. PCR array identified profilin1 (pfn1) mRNA as a major binding partner of HuR in neurons. HuR positively mediated the stability of pfn1 mRNA and influenced actin polymerization. Overexpression of Pfn1 successfully rescued the migration defects of HuR-deleted neurons. Our data revealed a posttranscriptional mechanism that maintains actin dynamics during neuronal migration.