title: Dopachrome tautomerase (Dct) regulates neural progenitor cell proliferation.
abstract: DOPAchrome tautomerase (Dct) functions downstream of tyrosinase in the biosynthetic pathway of eumelanin by catalyzing the conversion of dopachrome to 5,5-dihydroxyindole-2-carboxylic acid (DHICA) in pigment cells. Dct transcription is regulated directly or synergistically by Pax3, Sox10 and microphthalmia transcription factor (MITF). Using Dct-lacZ transgenic mice, we measured the spatial and temporal pattern of Dct expression in vivo during neocortical neurogenesis in the brain. Dct was expressed in all layers of the dorsal telencephalon in E10.5. At E15.5 and E17.5 when cortical neurogenesis occurs, expression of Dct was primarily localized to the ventricular zone (VZ) where neuronal stem cells reside. Blocking endogenous Dct by RNAi decreased proliferation of embryonic cortical neural progenitor cells (by 48%, P < 0.05), as determined by BrdU incorporation. In adult brain, Dct/Dct expression decreased in the subventricular zone (SVZ), dentate gyrus and olfactory bulb (OB). However, strong expression of Dct was observed in rostral migratory stream (RMS) and septum. Overexpression of Dct in SVZ cells derived from the adult mice significantly increased the number of cells by 260%, whereas silencing Dct by RNAi decreased cell numbers by 25.8% at 48 h post-nucleofection (P < 0.05). The results of RT-PCR analysis revealed that Dct in the brain lacks exon 7 and is identical to the form of Dct found in neural-crest-derived melanocytes. Our data indicate that Dct, previously known as a melanoblast marker, regulates neural progenitor cell proliferation.
authors.affiliation: Department of Neurology, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
authors.forename: Zhongxian
authors.initials: Z
authors.lastname: Jiao
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hornyak
authors.forename: Ann
authors.initials: A
authors.lastname: Hozeska
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Faith M
authors.initials: FM
authors.lastname: Strickland
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000502:physiology*; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*
chemical_list: D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase