mitfa is required at multiple stages of melanocyte differentiation but not to establish the melanocyte stem cell.
mitfa is required at multiple stages of melanocyte differentiation but not to establish the melanocyte stem cell.
复制标题
DOI：
10.1016/j.ydbio.2010.12.004
复制
发表时间：
2011-02-15
影响因子：
2.7
通讯作者：
Lister JA
中科院分区：
文献类型：
--
作者：
Johnson SL;Nguyen AN;Lister JA
mitfa基因编码的斑马鱼直系同源的小眼症相关的转录因子（Mitf），它像它的同行在其他物种中，是绝对需要的神经嵴黑色素细胞的发展。为了评估mitfa在黑素细胞发育不同阶段的作用，我们已经确定了mitfa的亚型等位基因，包括两个对黑素细胞发育温度敏感的等位基因。分子分析表明，mitffh 53 ts的结果从一个单一的碱基对的变化，产生一个天冬酰胺酪氨酸氨基酸取代的DNA结合域，和mitfavc 7 ts等位基因是一个剪接供体位点的突变，降低了正确剪接的转录水平。mitfavc 7等位基因的剪接本身似乎不是温度依赖性的。第三个亚纯型等位基因mitfaz 25导致蛋白质的第一螺旋结构域中的异亮氨酸被苯丙氨酸取代。用mitfafh 53 ts进行的升温实验表明，mitfa在黑素细胞分化的几个阶段都是必需的，包括早期成黑素细胞标记dct的表达，从dct表达到分化的进展，以及分化后树突状的维持。当在幼虫发育的所有阶段下调时，Mitfafh 53 TS突变体在2-3天内恢复黑素细胞。然而，当通过用erbB 3抑制剂AG 1478的早期处理来消融黑素细胞干细胞（MSC）时，黑素细胞恢复到48小时时丧失。该结果首先表明，MSC在限制温度下建立，并且在限制温度下保持约一天后，成黑素细胞死亡或丧失恢复能力。
The mitfa gene encodes a zebrafish ortholog of the microphthalmia-associated transcription factor (Mitf) which, like its counterparts in other species, is absolutely required for development of neural crest melanocytes. In order to evaluate mitfa’s role in different stages of melanocyte development, we have identified hypomorphic alleles of mitfa, including two alleles that are temperature-sensitive for melanocyte development. Molecular analysis revealed that the mitffh53ts results from a single base pair change producing an asparagine to tyrosine amino acid substitution in the DNA-binding domain, and the mitfavc7 ts allele is a mutation in a splice donor site that reduces the level of correctly-spliced transcripts. Splicing in the mitfavc7 allele does not itself appear to be temperature-dependent. A third, hypomorphic allele, mitfaz25 results in an isoleucine to phenylalanine substitution in the first helix domain of the protein. Temperature upshift experiments with mitfafh53ts show that mitfa is required at several stages of melanocyte differentiation, including for expression of the early melanoblast marker dct, again for progression from dct expression to differentiation, and again for maintenance of dendritic form following differentiation. mitfafh53ts mutants recover melanocytes within 2–3 days when downshifted at all stages of larval development. However, when melanocyte stem cells (MSCs) are ablated by early treatment with the erbB3 inhibitor AG1478, melanocyte recovery is lost by 48 hours. This result indicates first that the MSC is established at the restrictive temperature, and that melanoblasts die or lose the ability to recover after being held at the restrictive temperature for approximately one day.
登录
查看更多内容
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
11.4
作者：
FERREDAMARE, AR;POGNONEC, P;BURLEY, SK
通讯作者：
BURLEY, SK
影响因子：
2.7
作者：
Nechiporuk, A;Poss, KD;Keating, MT
通讯作者：
Keating, MT
影响因子：
2.7
作者：
Hultman, Keith A.;Johnson, Stephen L.
通讯作者：
Johnson, Stephen L.
影响因子：
10.5
作者：
Carreira, Suzanne;Goodall, Jane;Goding, Colin R.
通讯作者：
Goding, Colin R.