miR-126 modulates neural progenitor cell development

Abstract

Noncoding microRNAs (miRNAs) play important roles in controlling signaling pathways by targeting multiple genes and altering their expression levels. MiR-126 is a known endothelial-specific miRNA that regulates vascular integrity and angiogenesis by enhancing proangiogenic actions of VEGF and FGF. MiR-126 is also expressed in several stem cell compartments, including embryonic stem cell (ESC) and hematopoietic stem/progenitor cells (HSPC) where it regulates cell differentiation and quiescence. Here we show that miR-126 is expressed as well in neural progenitor cells where it regulates cell differentiation by targeting genes of the IGF1R signaling pathway including IRS1, PI3K and AKT. Moreover, Hoxa9 and IGF-1 expression by neural progenitor cells is upregulated when miR-126 expression levels are reduced. Our data, implicating a role for miR-126 in manipulating cell development, could open a window of opportunities for clinical purposes and therapeutic strategies to achieve controlling neural progenitor cell behavior. HighlightsO_LIKnockdown of miR-126 in neural progenitor cells increases cell proliferation C_LIO_LImiR-126 modulates expression levels of HoxA9 and known target genes involved in the IGF1R signaling pathway in neural progenitor cells C_LIO_LIOverexpression of miR-126 results in induced cell differentiation in neural progenitor cells C_LIO_LImiR-126 affects motor neuron development in the thoracic region of the spinal cord C_LIO_LIKnockdown of miR-126 expression results in increased IGF-1 expression C_LI