NOV/CCN3 promotes maturation of cerebellar granule neuron precursors

A body of evidence points to the matricial CCN proteins as key regulators of organogenesis. NOV/CCN3, a founder CCN member, is expressed in the developing central nervous system but its functions during neural development have not been studied yet. Here we describe the pattern of NOV expression during rat cerebellar postnatal development and show that NOV expression increases during the second postnatal week, a critical period for the maturation of granule neuron precursors (GNP). NOV transcripts are specifically produced by Purkinje neurons and NOV protein localises extracellularly in the molecular layer and the inner part of the external granule layer, at a key position to control GNP proliferation and migration. In vitro, NOV reduces Sonic Hedgehog-induced GNP proliferation through beta3 integrins and stimulation of GSK3-beta activity whereas NOV stimulates GNP migration through distinct RGD-dependent integrins. These findings identify a new paracrine role of NOV in the development of cerebellar granule neurons.