MicroRNA-9 Reveals Regional Diversity of Neural Progenitors along the Anterior-Posterior Axis

Summary

Neural progenitors self-renew and generate neurons throughout the central nervous system. Here, we uncover an unexpected regional specificity in the properties of neural progenitor cells, revealed by the function of a microRNA—miR-9. miR-9 is expressed in neural progenitors, and its knockdown results in an inhibition of neurogenesis along the anterior-posterior axis. However, the underlying mechanism differs—in the hindbrain, progenitors fail to exit the cell cycle, whereas in the forebrain they undergo apoptosis, counteracting the proliferative effect. Among several targets, we functionally identify hairy1 as a primary target of miR-9, regulated at the mRNA level. hairy1 mediates the effects of miR-9 on proliferation, through Fgf8 signaling in the forebrain and Wnt signaling in the hindbrain, but affects apoptosis only in the forebrain, via the p53 pathway. Our findings show a positional difference in the responsiveness of progenitors to miR-9 depletion, revealing an underlying divergence of their properties.

Highlights

► miR-9 function in neural progenitors is context dependent ► miR-9 loss induces proliferation in the hindbrain and apoptosis in the forebrain ► The primary function of miR-9 in neurogenesis is to downregulate hairy1 mRNA levels ► miR-9/ hairy1 affects proliferation via cyclinD/p27 and apoptosis via p53