Nrsf silencing induces molecular and subcellular changes linked to neuronal plasticity.

Neurite outgrowth involves various molecular mechanisms generating complex brain connections. These mechanisms have been linked to plasticity and learning and are thought to be deregulated in neuropsychiatric diseases. The transcription factor REST/NRSF regulates a subset of genes encoding neurite outgrowth molecules. We demonstrate here the downregulation of Rest/Nrsf expression in a mouse neuroblastoma cell line. This downregulation induced a clear increase in neurite length. Quantitative polymerase chain reaction showed deregulation of the candidate genes L1cam, Elmo2, Ulip1 and Ulip2. These genes are bona fide candidates known to be involved in dendrite and axonal outgrowth. This approach could be adapted to high-throughput techniques for determination of the mammalian neurite outgrowth gene repertoire.