Isolation and developmental expression of Mitf in Xenopus laevis

Mitf (gene for microphthalmia-associated transcription factor) encodes a transcription factor of the basic/helix-loop-helix/leucine-zipper family and is a key regulator during the development of two different types of melanin-producing cell lineages, namely neural crest-derived melanocytes/melanophores, and the retinal pigment epithelium (RPE) differentiated from the outer layer of the eye cup. Mitf-deficient mice show a lack of melanocytes and small eyes caused by abnormal RPE development. An interesting feature of Mitf is the existence of multiple isoforms with different amino termini and their functions in the development of these melanin-producing pigment cells. In this study, we isolated two Mitf homologues (XlMitfalpha and XlMitfbeta) and their isoforms from Xenopus laevis. Alignment analysis of the amino acid sequences of the N-termini suggests that these isoforms are homologues of mouse Mitf-M (expressed specifically in the melanocyte lineage) and Mitf-A (strongly expressed in the RPE, although this expression is ubiquitous). In Xenopus, XlMitfalpha is strongly expressed in the melanophore lineage (especially in premigratory melanoblasts) and the presumptive RPE and the epiphysis, in which melanin-producing cells differentiate in some vertebrates. Conservation of the Mitf isoforms expected to possess specific functions in the development of melanin-producing cells and of the expressions in such cell types in Xenopus suggest that XlMitf plays a central role in the development of melanin-producing cell lineages, and that, as in mice and humans, most of the signaling molecules or transcription factors implicated genetically in the development of melanin-producing cell lineages affect either Mitf expression or its function (Goding [2000] Genes Dev. 14:1712-1728).