Epigenetic modification of vomeronasal (V2r) precursor neurons by histone deacetylation

• Published in: Neuroscience 2010-09, Vol.169 (3), p.1462-1472
• Main Authors: Xia, J, Broad, K.D, Emson, P.C, Keverne, E.B
• Format: Article
• Language: English
• Subjects: Animals; Axon guidance; Biological and medical sciences; Cell Differentiation; Cells, Cultured; Epigenesis, Genetic; epigenetic regulation; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Genetic Markers; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - metabolism; Hydroxamic Acids - pharmacology; Mice; Microtubule-Associated Proteins - biosynthesis; mouse; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; neurogenesis; Neurology; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Oligonucleotide Array Sequence Analysis; Receptors, Pheromone - biosynthesis; Receptors, Pheromone - genetics; Transcription, Genetic; Valproic Acid - pharmacology; Vertebrates: nervous system and sense organs; VNO; vomeronasal organ; Vomeronasal Organ - cytology; Vomeronasal Organ - metabolism
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.05.071

Abstract Vomeronasal neurons undergo continuous neurogenesis throughout development and adult life. These neurons originate as stem cells in the apical zone of the lumen of the vomeronasal organ (VNO) and are described as nestin-expressing glia-like progenitor cells ( Murdoch and Roskams, 2008 ). They then migrate horizontally along the basal zone where they differentiate into functional VNO neurons ( Kaba et al., 1988 ). We harvested progenitor cells from the adult VNO and, after 3–6 months of invitro culture, these VNO neurons remained in a stable undifferentiated state expressing nestin, β-tubulin III and vomeronasal type 2 (V2r), but not vomeronasal type 1 (V1r) receptors. Application of histone-deacetylase inhibitors induced development of a neural phenotype that expressed V2r receptors, a down-regulation of nestin expression and no change in any specific genetic markers associated with glial cells. Treatment with valproic acid induced extensive changes in gene expression in the axon guidance pathway. The adult VNO is known to functionally adapt throughout life as a consequence of changes in both a mouse's physiological status and its social environment. These pluripotent cultured neurons may provide valuable insights into how changes in both physiology and environment, exert epigenetic effects on vomeronasal neurons as they undergo continuous neurogenesis and development throughout the life of a mouse.