Altered melanocyte differentiation and retinal pigmented epithelium transdifferentiation induced by Mash1 expression in pigment cell precursors.
Transcription factor genes governing pigment cell development that are associated with spotting mutations in mice include members of several structural transcription factor classes but not members of the basic helix-loop-helix (bHLH) class, important for neurogenesis and myogenesis. To determine the effects of bHLH factor expression on pigment cell development, the neurogenic bHLH factor Mash1 was expressed early in pigment cell development in transgenic mice from the dopachrome tautomerase (Dct) promoter. Dct:Mash1 transgenic founders exhibit variable microphthalmia and patchy coat color hypopigmentation. Transgenic F1 mice exhibit microphthalmia with complete coat color dilution. Marker analysis demonstrates that Mash1 expression in the retinal pigmented epithelium (RPE) initiates neurogenesis in this cell layer, whereas expression in remaining neural crest-derived melanocytes alters their differentiation, in part by profoundly downregulating expression of the p (pink-eyed dilution) gene, while maintaining their cell fate. The effects of transcriptional perturbation of pigment cell precursors by Mash1 further highlight differences between pigment cells of distinct developmental origins, and suggest a mechanism for the alteration of melanogenesis to result in marked coat color dilution.
Lanning
Jessica L
JL
Department of Dermatology, Henry Ford Health System, Detroit, Michigan, USA.
Wallace
Jaclyn S
JS
Zhang
Deming
D
Diwakar
Ganesh
G
Jiao
Zhongxian
Z
Hornyak
Thomas J
TJ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000502:physiology; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology; D010857:Pigment Epithelium of Eye / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D019076:Transgenes
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D019746:Intramolecular Oxidoreductases; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C042501:dopachrome isomerase