Hnrnpab regulates neural cell motility through transcription of Eps8

Cell migration requires a complicated network of structural and regulatory proteins. Changes in cellular motility can impact migration as a result of cell-type or developmental stage regulated expression of critical motility genes. Hnrnpab is a conserved RNA-binding protein found as two isoforms produced by alternative splicing. Its expression is enriched in the subventricular zone (SVZ) and the rostral migratory stream within the brain, suggesting possible support of the migration of neural progenitor cells in this region. Here we show that the migration of cells from the SVZ of developing Hnrnpab(−/−) mouse brains is impaired. An RNA-seq analysis to identify Hnrnpab-dependent cell motility genes led us to Eps8, and in agreement with the change in cell motility, we show that Eps8 is decreased in Hnrnpab(−/−) SVZ tissue. We scrutinized the motility of Hnrnpab(−/−) cells and confirmed that the decreases in both cell motility and Eps8 are restored by ectopically coexpressing both alternatively spliced Hnrnpab isoforms, therefore these variants are surprisingly nonredundant for cell motility. Our results support a model where both Hnrnpab isoforms work in concert to regulate Eps8 transcription in the mouse SVZ to promote the normal migration of neural cells during CNS development.