The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.
The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.
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DOI：
10.1016/j.ydbio.2013.01.004
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发表时间：
2013-03-15
影响因子：
2.7
通讯作者：
Pavan, William J.
中科院分区：
文献类型：
--
作者：
Silver, Debra L.;Leeds, Karen E.;Hwang, Hun-Way;Miller, Emily E.;Pavan, William J.
黑素母细胞是一群神经嵴来源的细胞，它们产生我们身体中产生色素的细胞。黑素母细胞发育和功能缺陷是包括瓦尔登堡综合征和黑色素瘤在内的许多疾病的基础。了解黑素母细胞发育的遗传规律将有助于阐明这些和其他神经营养不良疾病的病因。在这里，我们证明了外显子连接复合体的一个组成部分Magoh是正常的黑素母细胞发育所必需的。Magoh haplo不足的小鼠色素减少，并与转录因子Sox10表现出强大的遗传相互作用。这些表型是由胚胎发育中期开始的黑素母细胞数量显著减少引起的。引人注目的是，虽然Magoh单倍体功能不全严重减少了表皮黑素母细胞，但它并没有显著影响真皮黑素母细胞的数量。这些数据表明，Magoh通过不成比例地影响表皮黑素母细胞种群的扩张来影响黑素母细胞的发育。我们探索了黑素母细胞减少的细胞学基础，发现Magoh突变的黑素母细胞并没有经历更多的凋亡，而是被阻止在有丝分裂中。在Magoh单倍体不足的胚胎和经Magoh siRNA处理的黑色素瘤细胞系中，有丝分裂停止是明显的。综上所述，我们的发现表明，Magoh调控的真皮黑素母细胞增殖可能是产生表皮结合的黑素母细胞的关键。我们的结果指出了Magoh在黑素细胞发育中的核心作用。
Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waarden burg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haplo insufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development.
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影响因子：
4.5
作者：
Silver DL;Hou L;Somerville R;Young ME;Apte SS;Pavan WJ
通讯作者：
Pavan WJ
影响因子：
21.3
作者：
Kittler, Ralf;Pelletier, Laurence;Buchholz, Frank
通讯作者：
Buchholz, Frank
影响因子：
64.5
作者：
Adameyko, Igor;Lallemend, Francois;Ernfors, Patrik
通讯作者：
Ernfors, Patrik
影响因子：
--
作者：
Prasad MK;Reed X;Gorkin DU;Cronin JC;McAdow AR;Chain K;Hodonsky CJ;Jones EA;Svaren J;Antonellis A;Johnson SL;Loftus SK;Pavan WJ;McCallion AS
通讯作者：
McCallion AS
影响因子：
4.6
作者：
Luciani, Flavie;Champeval, Delphine;Delmas, Veronique
通讯作者：
Delmas, Veronique