Transcriptional regulation of proteins involved in neuronal polarity is a key process that underlies the ability of neurons to transfer information in the central nervous system. The Collapsin Response Mediator Protein (CRMP) family is best known for its role in neurite outgrowth regulation conducting to neuronal polarity and axonal guidance, including CRMP5 that drives dendrite differentiation. Although CRMP5 is able to control dendritic development, the regulation of its expression remains poorly understood. Here we identify a Sox5 consensus binding sequence in the putative promoter sequence upstream of the CRMP5 gene. By luciferase assays we show that Sox5 increases CRMP5 promoter activity, but not if the putative Sox5 binding site is mutated. We demonstrate that Sox5 can physically bind to the CRMP5 promoter DNA in gel mobility shift and chromatin immunoprecipitation assays. Using a combination of real-time RT-PCR and quantitative immunocytochemistry, we provide further evidence for a Sox5-dependent upregulation of CRMP5 transcription and protein expression in N1E115 cells: a commonly used cell line model for neuronal differentiation. Furthermore, we report that increasing Sox5 levels in this neuronal cell line inhibits neurite outgrowth. This inhibition requires CRMP5 because CRMP5 knockdown prevents the Sox5-dependent effect. We confirm the physiological relevance of the Sox5-CRMP5 pathway in the regulation of neurite outgrowth using mouse primary hippocampal neurons. These findings identify Sox5 as a critical modulator of neurite outgrowth through the selective activation of CRMP5 expression.

The MiT-TFE family of transcription factors consists of the MITF, TFEB, TFE3, and TFEC proteins (Hemesath et al., 1994; Hodgkinson, et al., 1993). They all share the common basic helix-loop-helix leucine zipper (bHLH-Zip) motif required for dimerization and DNA binding as well as a couple of other functional domains including transactivation and nuclear translocation domains (reviewed in Goding &

Melanocytes originate in the neural crest as precursor cells which then migrate and proliferate to reach their destination where they differentiate into pigment-producing cells.Melanocytes not only determine the color of hair, skin and eyes but also protect against the harmful effects of UV irradiation. The establishment of the melanocyte lineage is regulated by a defined set of transcription factors and signaling pathways that direct the specific gene expression programs underpinning melanoblast specification, survival, migration, proliferation and differentiation. In addition, epigenetic modifiers and replacement histones play key roles in regulating gene expression and its timing during the different steps of this process. Here we discuss the evidence for the role of epigenetic regulators in melanocyte development and function and how they interact with transcription factors and signaling pathways to establish and maintain this important cell lineage.