Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
Genes Cells. 2015 May;20(5):439-49. doi: 10.1111/gtc.12235. Epub 2015 Mar 27.
Neural crest cells (NCCs) emerge from the dorsal region of the neural tube of vertebrate embryos and have the pluripotency to differentiate into both neuronal and non-neuronal lineages including melanocytes. Rest, also known as NRSF (neuro-restrictive silencer factor), is a regulator of neuronal development and function and suggested to be involved in the lineage specification of NCCs. However, further investigations of Rest gene functions in vivo have been hampered by the fact that Rest null mice show early embryonic lethality. To investigate the function of Rest in NCC development, we recently established NCC-specific Rest conditional knockout (CKO) mice and observed their neonatal death. Here, we have established viable heterozygous NCC-specific Rest CKO mice to analyze the function of Rest in an NCC-derived melanocyte cell lineage and found that the white spotting phenotype was associated with the reduction in the number of melanoblasts in the embryonic skin. The Rest deletion induced after the specification to melanocytes did not reduce the number of melanoblasts; therefore, the expression of REST during the early neural crest specification stage was necessary for the normal development of melanoblasts to cover all of the skin.
神经嵴细胞（NCCs）起源于脊椎动物胚胎神经管的背侧区域，具有多能性，可以分化为神经元和非神经元谱系，包括黑色素细胞。静止因子（Rest），也称为 NRSF（神经限制沉默因子），是神经元发育和功能的调节剂，被认为参与 NCC 的谱系特化。然而，由于 Rest 基因缺失的小鼠在胚胎早期就会死亡，因此对 Rest 基因在体内的功能进行进一步研究受到了阻碍。为了研究 Rest 在 NCC 发育中的作用，我们最近建立了 NCC 特异性的 Rest 条件性敲除（CKO）小鼠，并观察到它们在新生时死亡。在这里，我们建立了存活的杂合 NCC 特异性 Rest CKO 小鼠，以分析 Rest 在 NCC 衍生的黑色素细胞谱系中的功能，发现白色斑点表型与胚胎皮肤中黑色素母细胞数量的减少有关。黑色素细胞特化后诱导的 Rest 缺失并没有减少黑色素母细胞的数量；因此，在早期神经嵴特化阶段表达 REST 对于黑色素母细胞的正常发育以覆盖所有皮肤是必要的。
