Endothelin 3 induces the reversion of melanocytes to glia through a neural crest-derived glial-melanscytic progenitor
Endothelin 3 induces the reversion of melanocytes to glia through a neural crest-derived glial-melanscytic progenitor
复制标题
DOI：
10.1073/pnas.97.14.7882
复制
发表时间：
2000-07-05
影响因子：
11.1
通讯作者：
Le Douarin, NM
中科院分区：
文献类型：
--
作者：
Dupin, E;Glavieux, C;Le Douarin, NM
内皮素3 （ET3）及其受体B （ETRB）的功能信号传导已被证明是小鼠神经嵴（NC）衍生色素细胞发育所必需的，但ET3的确切作用尚不完全清楚。以禽类胚胎为模型，我们之前报道了ET3促进主干NC培养中单能性黑素细胞和双能性胶质-黑素细胞前体的存活和增殖。在这里，我们研究了胚胎色素细胞是否在后期对ET3有反应。先前的研究结果支持了这种可能性，即在体内，鸟类黑色素细胞在迁移过程中和皮肤分化后表达内皮素受体B2 （ETRB2）。我们发现，在体外，ET3对胚胎鹌鹑背皮肤表皮上的NC细胞的增殖和黑色素形成产生剂量依赖性刺激。此外，在皮肤源性色素细胞的克隆培养中，ET3诱导克隆源性黑色素细胞的快速细胞分裂，产生黑色素细胞和缺乏色素颗粒的细胞的混合后代，并在超过40%的菌落中表达胶质标记物。因此，我们可以得出结论，ET3对胚胎色素细胞具有强烈的有丝分裂性，并能够改变它们的分化程序，导致它们重现其NC祖先的胶质-黑素细胞双电位。
Functional signaling of endothelin 3 (ET3) and its receptor B (ETRB) has been shown to be required for the development of neural crest (NC)-derived pigment cells in mouse, but the precise role of ET3 is not completely understood. Using the avian embryo as a model, we previously reported that ET3 promotes the survival and proliferation of unipotent melanocyte and bipotent glia-melanocyte precursors in trunk NC cultures. Here we investigated whether, at later stages, embryonic pigment cells respond to ET3. Such a possibility is supported by the previous finding that, in vivo, avian melanocytes express endothelin receptor B2 (ETRB2) during migration and after their differentiation in the skin. We found that in vitro ET3 exerts a dose-dependent stimulation of proliferation and melanogenesis in NC cells that had homed to the epidermis of embryonic quail dorsal skin. Moreover, in clonal cultures of skin-derived pigment cells, ET3 induces rapid cell divisions of clonogenic melanocytes that generate a mixed progeny of melanocytes and cells devoid of pigment granules and expressing glial markers in more than 40% of the colonies. It can therefore be concluded that ET3 is strongly mitogenic to embryonic pigment cells and able to alter their differentiation program, leading them to recapitulate the glial-melanocyte bipotentiality of their NC ancestors.