title: EMX homeobox genes regulate microphthalmia and alter melanocyte biology.
abstract: Melanocytes are specialized cells that produce melanin, the pigment responsible for skin, hair and retina color. They derive during embryogenesis from the precursor cells melanoblasts, which are neural crest cells committed to the pigment cell lineage. The differentiation of melanoblasts into melanocytes involves the expression of melanocyte-specific genes, particularly those responsible for melanin production, such as Tyr, Tyrp-1 and Dct, the expression of which depends on the melanocyte-specific transcription factor microphthalmia (Mitf). We have developed and executed a functional screen on melanocytes, with the aim of identifying genes involved in pigment cell biology. We have found Emx1 and Emx2, two highly related homeobox genes that when overexpressed in melanocytes can downregulate Mitf, Tyrp1, Dct and Tyr. Constitutive expression of Emx alters pigment cell morphology and growth properties: it confers TPA independence but not the ability to grow in soft agar. Spatial and temporal expression of Emx and Mitf during embryonic development suggests that Emx could be one factor that regulates correct expression of Mitf by inhibiting its activation in neuroepithelial derivatives other than melanocytes.
authors.affiliation: Wolfson Institute for Biomedical Research, London WC1E 6BT, UK.
authors.forename: Walter
authors.initials: W
authors.lastname: Bordogna
authors.forename: James D
authors.initials: JD
authors.lastname: Hudson
authors.forename: Joanna
authors.initials: J
authors.lastname: Buddle
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Bennett
authors.forename: David H
authors.initials: DH
authors.lastname: Beach
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D008850:Microphthalmos / Q000235:genetics / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000196:embryology; D011725:Pyridines / Q000494:pharmacology; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D018398:Homeodomain Proteins; D019746:Intramolecular Oxidoreductases; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase; D010088:Oxidoreductases; D011725:Pyridines; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C497235:Mitf protein, mouse; C431843:tris(2-pyridylmethyl)amine; C079621:Tyrp1 protein, mouse; C042501:dopachrome isomerase