Isolation and developmental expression of Mitf in Xenopus laevis

Isolation and developmental expression of Mitf in Xenopus laevis
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DOI:
10.1002/dvdy.20019
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发表时间:
2004-05-01
影响因子:
2.5
通讯作者:
Yamamoto, H
Yamamoto, H
中科院分区:
生物学3区
文献类型:
--
作者:
Kumasaka, M;Sato, H;Yamamoto, H

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Mitf(小眼相关转录因子基因)编码碱性/螺旋-环-螺旋/亮氨酸-zipper家族的转录因子,是两种不同类型的黑色素产生细胞系发育过程中的关键调节因子,即神经嵴来源的黑色素细胞/黑色素细胞,以及从眼杯外层分化的视网膜色素上皮(RPE)。mitf缺陷小鼠由于RIPE发育异常导致黑色素细胞缺失和小眼睛。Mitf的一个有趣的特征是存在多个具有不同氨基末端的同工异构体及其在这些产生黑色素的色素细胞的发育中的功能。本研究从非洲爪蟾中分离出两个Mitf同源物(XlMitfalpha和XlMitfbeta)及其同型异构体。对n端氨基酸序列的比对分析表明,这些同型异构体是小鼠Mitf-M(在黑素细胞谱系中特异性表达)和Mitf-A(在RPE中强烈表达,尽管这种表达普遍存在)的同源物。在非洲爪蟾中,XlMitfalpha在黑素细胞谱系(特别是在迁移前的黑素母细胞中)、推测的RPE和一些脊椎动物的黑色素生成细胞分化的骨骺中强烈表达。在非洲爪蟾中,Mitf同种异构体在黑色素产生细胞的发育和这种细胞类型的表达中具有特定的功能,这表明XlMitf在黑色素产生细胞谱系的发育中起着核心作用,并且,与小鼠和人类一样,大多数与黑色素产生细胞系发育有关的信号分子或转录因子影响Mitf的表达或其功能(Goding[2000] .基因学报,14:1712-1728)。Wiley-Liss, Inc.
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 RIPE 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). (C) Wiley-Liss, Inc.