The zebrafish sf3b1b460 mutant reveals differential requirements for the sf3b1 pre-mRNA processing gene during neural crest development
The zebrafish sf3b1b460 mutant reveals differential requirements for the sf3b1 pre-mRNA processing gene during neural crest development
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DOI：
10.1387/ijdb.113383ma
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发表时间：
2012-01-01
影响因子：
0.7
通讯作者：
Henion, Paul D.
中科院分区：
文献类型：
--
作者：
An, Min;Henion, Paul D.
控制胚胎细胞多样化的基因调控网络的功能发生在遗传相互作用的阐述所必需的组成型活性分子机制的背景上。这种“管家”基因的子集在调节发育的特定方面中的重要作用已变得越来越清楚。前mRNA加工对于通过例如内含子的切除产生功能性转录物是必不可少的。我们克隆了斑马鱼吐司（b460）基因座，发现它编码剪接因子3b亚基1（sf3b1）。sf3b1（b460）突变导致sf3b1的异常剪接，导致功能性和预测的非功能性转录本和全长Sf3b1蛋白减少90%。sf3b1（b460）突变分离的诱变筛选的基础上缺乏神经嵴衍生的黑色素细胞。进一步的分析显示，具体的早期缺陷，神经嵴的发展，而其他外胚层人口的早期发展似乎不受影响。神经嵴发育的基本转录调节因子的表达在sf3b1（b460）突变体中被严重破坏，部分原因是这些因子的一个子集的前mRNA加工缺陷，导致神经嵴亚系规范，存活和迁移的缺陷。这些因子的一个子集的错误表达挽救了突变胚胎中神经嵴发育的各个方面。我们的研究结果表明，虽然sf3b1是一个无处不在的必需基因，它所需要的程度表现出组织类型的特异性在早期胚胎发生。此外，sf3b1（b460）突变引起的发育缺陷提供了控制神经嵴发育的基因调控网络成员之间的遗传相互作用的见解。
The functions of gene regulatory networks that control embryonic cell diversification occur on a background of constitutively active molecular machinery necessary for the elaboration of genetic interactions. The essential roles of subsets of such "housekeeping" genes in the regulation of specific aspects of development have become increasingly clear. Pre-mRNA processing is essential for production of functional transcripts by, for example, excision of introns. We have cloned the zebrafish toast(b460) locus and found that it encodes splicing factor 3b, subunit 1 (sf3b1). The sf3b1(b460) mutation causes aberrant splicing of sf3b1 resulting in functional and predicted non-functional transcripts and a 90% reduction in full-length Sf3b1 protein. The sf3b1(b460) mutation was isolated in a mutagenesis screen based on the absence of neural crest-derived melanophores. Further analysis revealed specific earlier defects in neural crest development, whereas the early development of other ectodermal populations appears unaffected. The expression of essential transcriptional regulators of neural crest development are severely disrupted in sf3b1(b460) mutants, due in part to defects in pre-mRNA processing of a subset of these factors, leading to defects in neural crest sublineage specification, survival and migration. Misexpression of a subset of these factors rescues aspects of neural crest development in mutant embryos. Our results indicate that although sf3b1 is a ubiquitously essential gene, the degree to which it is required exhibits tissue-type specificity during early embryogenesis. Further, the developmental defects caused by the sf3b1(b460) mutation provide insights into genetic interactions among members of the gene regulatory network controlling neural crest development.