microRNA regulation of neural precursor self-renewal and differentiation

During early stages of development of the vertebrate central nervous system, neural precursors divide symmetrically to produce new precursors, thereby expanding the precursor population. During middle stages of neural development, precursors switch to an asymmetric division pattern whereby each mitosis produces one new precursor and one cell that differentiates as a neuron or glial cell. At late stages of development, most precursors stop dividing and terminally differentiate. Par complex proteins are associated with the apical membrane of neural precursors and promote precursor self-renewal. How Par proteins are down regulated to bring precursor self-renewal to an end has not been known. Our investigations of zebrafish neural development revealed that the microRNA miR-219 negatively regulates apical Par proteins, thereby promoting cessation of neural precursor division and driving terminal differentiation.