colgate/hdac1 repression of foxd3 expression is required to permit mitfa-dependent melanogenesis
colgate/hdac1 repression of foxd3 expression is required to permit mitfa-dependent melanogenesis
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DOI：
10.1016/j.ydbio.2007.10.045
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发表时间：
2008-01-15
影响因子：
2.7
通讯作者：
Henion, Paul D.
中科院分区：
文献类型：
--
作者：
Ignatius, Myron S.;Moose, Holly E.;Henion, Paul D.
神经嵴源性色素细胞的发育已被广泛用于研究细胞的命运规范、迁移、增殖、存活和分化。色素细胞发育所需的许多基因和调控机制在脊椎动物中是保守的。斑马鱼突变体高露脂(col)/组蛋白去乙酰化酶1 （hdac1）减少了神经嵴来源的黑色素细胞及其前体的数量，延迟了分化和迁移。在hdac1（col）突变体中，诱导正常数量的预迁移神经嵴细胞。后来，虽然hdac1（col）突变体的神经嵴细胞数量只有轻微减少，但mitfa阳性的黑素母细胞数量却严重减少，这表明hdac1是黑素母细胞规范所必需的。与此同时，hdac1（col）突变体神经嵴细胞中foxd3的表达显著增加并延长。我们发现，部分降低hdac1（col）突变体中Foxd3的表达可以挽救hdac1（col）突变体中mitfa的表达和黑素细胞缺陷。此外，我们证明了Foxd3在mitfa启动子上进行物理相互作用的能力。由于mitfa是黑素母细胞发育和发育所必需的，我们的研究结果表明，hdac1通常需要抑制神经嵴foxd3的表达，从而去抑制mitfa，导致一部分神经嵴来源的细胞发生黑色素。(C) 2007爱思唯尔公司版权所有。
Neural crest-derived pigment cell development has been used extensively to study cell fate specification, migration, proliferation, survival and differentiation. Many of the genes and regulatory mechanisms required for pigment cell development are conserved across vertebrates. The zebrafish mutant colgate (col)/histone deacetylase1 (hdac1) has reduced numbers, delayed differentiation and decreased migration of neural crest-derived melanophores and their precursors. In hdac1(col) mutants normal numbers of premigratory neural crest cells are induced. Later, while there is only a slight reduction in the number of neural crest cells in hdac1(col) mutants, there is a severe reduction in the number of mitfa-positive melanoblasts suggesting that hdac1 is required for melanoblast specification. Concomitantly, there is a significant increase in and prolonged expression of foxd3 in neural crest cells in hdac1(col) mutants. We found that partially reducing Foxd3 expression in hdac1(col) mutants rescues mitfa expression and the melanophore defects in hdac1(col) mutants. Furthermore, we demonstrate the ability of Foxd3 to physically interact at the mitfa promoter. Because mitfa is required for melanoblast specification and development, our results suggest that hdac1 is normally required to suppress neural crest foxd3 expression thus de-repressing mitfa resulting in melanogenesis by a subset of neural crest-derived cells. (C) 2007 Elsevier Inc. All rights reserved.