Role of miRNA-9 in Brain Development

Abstract

MicroRNAs (miRNAs) are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9) is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In this article, the role of miR-9 in the developing forebrain (telencephalon and diencephalon), midbrain, hindbrain, and spinal cord of vertebrate species is highlighted. In the forebrain, miR-9 is necessary for the proper development of dorsoventral telencephalon by targeting marker genes expressed in the telencephalon. It regulates proliferation in telencephalon by regulating Foxg1, Pax6, Gsh2, and Meis2 genes. The feedback loop regulation between miR-9 and Nr2e1/Tlx helps in neuronal migration and differentiation. Targeting Foxp1 and Foxp2, and Map1b by miR-9 regulates the radial migration of neurons and axonal development. In the organizers, miR-9 is inversely regulated by hairy1 and Fgf8 to maintain zona limitans interthalamica and midbrain-hindbrain boundary (MHB). It maintains the MHB by inhibiting Fgf signaling genes and is involved in the neurogenesis of the midbrain-hindbrain by regulating Her genes. In the hindbrain, miR-9 modulates progenitor proliferation and differentiation by regulating Her genes and Elav3. In the spinal cord, miR-9 modulates the regulation of Foxp1 and Onecut1 for motor neuron development. In the forebrain, midbrain, and hindbrain, miR-9 is necessary for proper neuronal progenitor maintenance, neurogenesis, and differentiation. In vertebrate brain development, miR-9 is involved in regulating several region-specific genes in a spatiotemporal pattern.