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J. Biol. Chem., Vol. 279, Issue 40, 41911-41917, October 1, 2004

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Microphthalmia Transcription Factor Induces Both Retinal Pigmented Epithelium and Neural Crest Melanocytes from Neuroretina Cells^*

Nathalie Planque, Graça Raposo¶, Laurence Leconte, Oceane Anezo, Patrick Martin||, and Simon Saule**

From the UMR 146, Institut Curie Section de Recherche, Btiment 110, Centre Universitaire 91405 Orsay Cedex and the ^¶UMR 144, Institut Curie, Section de Recherche, 26 Rue d'Ulm, 75231 Paris, cedex 05 France

Mitf encodes a basic helix-loop-helix transcription factor that plays an essential role in the differentiation of the retinal pigmented epithelium (RPE) and neural crest-derived melanocytes. As cells containing melanogenic enzymes (TRP2) are found in Mitf mouse mutants, it is not clear whether Mitf is a downstream factor or a master regulator of melanocyte differentiation. To further study the role of Mitf in committing cells to the melanocyte lineage, we express Mitf in the cultured quail neuroretina cells. This leads to the induction of two types of pigmented cells: neural crest-derived melanocytes, according to their dendritic morphology, physiology, and gene expression pattern are observed together with pigmented epithelial RPE-like cells. The expression of Mitf is lower in pigmented epithelial RPE-like cells than in neural crest-derived melanocytes. Accordingly, overexpression of Mitf in cultured quail RPE causes cells to develop into neural crest-like pigmented cells. Thus, Mitf is sufficient for the proper differentiation of crest-like pigmented cells from retinal cells and its expression level may determine the type of pigment cell induced.

Received for publication, May 4, 2004 , and in revised form, July 9, 2004.

^* This work was supported by grants from the CNRS, the Institut Curie, the Association Retina France, and the Association pour la Recherche Contre le Cancer. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Laboratoire d'Oncologie Virale et Moléculaire Université Paris 7, case 7048 Tour 54, 5ème étage, couloir 54–64, pièce 12 2 place Jussieu, 75005 Paris, France.

^|| Present address: CNRS UMR6548, Transcriptional Regulation and Differentiation Btiment Sciences Naturelles-Niveau 3 Parc Valrose, Université de Nice 06108, Nice cedex 02, France.

^** To whom correspondence should be addressed: UMR 146, Institut Curie Section de Recherche, Btiment 110, Centre Universitaire 91405 Orsay Cedex, France. Tel.: 33-1-69-86-71-53; Fax: 33-1-69-07-45-25; E-mail: Simon.Saule{at}curie.u-psud.fr.

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