Bordogna Walter, Hudson James D, Buddle Joanna, Bennett Dorothy C, Beach David H, Carnero Amancio
Wolfson Institute for Biomedical Research, London WC1E 6BT, UK.
Exp Cell Res. 2005 Nov 15;311(1):27-38. doi: 10.1016/j.yexcr.2005.08.013. Epub 2005 Sep 27.
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.
黑素细胞是产生黑色素的特殊细胞，黑色素是负责皮肤、毛发和视网膜颜色的色素。它们在胚胎发生过程中源自前体细胞黑素母细胞，黑素母细胞是致力于色素细胞谱系的神经嵴细胞。黑素母细胞向黑素细胞的分化涉及黑素细胞特异性基因的表达，特别是那些负责黑色素产生的基因，如Tyr、Tyrp-1和Dct，它们的表达取决于黑素细胞特异性转录因子小眼畸形相关转录因子（Mitf）。我们已经开发并实施了一项针对黑素细胞的功能筛选，目的是鉴定参与色素细胞生物学的基因。我们发现了Emx1和Emx2，这两个高度相关的同源盒基因，当在黑素细胞中过表达时，它们可以下调Mitf、Tyrp1、Dct和Tyr。Emx的组成型表达改变了色素细胞的形态和生长特性：它赋予细胞对佛波酯（TPA）的独立性，但不赋予其在软琼脂中生长的能力。Emx和Mitf在胚胎发育过程中的时空表达表明，Emx可能是通过抑制其在黑素细胞以外的神经上皮衍生物中的激活来调节Mitf正确表达的一个因素。
