The role of Sox6 in zebrafish muscle fiber type specification.
The role of Sox6 in zebrafish muscle fiber type specification.
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DOI：
10.1186/s13395-014-0026-2
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发表时间：
2015
期刊：
影响因子：
4.9
通讯作者：
Ingham PW
中科院分区：
文献类型：
--
作者：
Jackson HE;Ono Y;Wang X;Elworthy S;Cunliffe VT;Ingham PW
转录因子Sox 6参与调节哺乳动物肌纤维类型特异性基因表达。在斑马鱼中，转录因子Prdm1a的功能丧失导致慢肌纤维类型向快肌纤维类型的转变，这是由慢肌纤维祖细胞中sox6的异位表达所预示的。吗啉代介导的Sox6敲低可以抑制这种转化，但只导致三个慢收缩特异性基因之一的异位表达。在这里，我们使用功能的增益和损失分析，进一步分析Sox 6在斑马鱼肌纤维类型特化中的作用。利用GAL 4二元错表达系统在斑马鱼胚胎中异位表达Sox 6。顺式调控元件的特点是使用转基因鱼。利用锌指核酸酶介导的定点突变技术，分析了斑马鱼胚胎、仔鱼和成体Sox 6基因功能缺失的影响。GCaMP3钙报告基因转基因斑马鱼用于测定野生型和突变体肌纤维中的Ca2+瞬变。异位Sox6表达足以下调斑马鱼胚胎中慢收缩特异性基因的表达。顺式调控元件上游的慢肌球蛋白重链1（smyhc1）和慢肌钙蛋白C（tnnc1b）基因含有推定的Sox 6结合位点所需的镇压，但不是后者。胚胎纯合sox6零等位基因表达tnnc1b整个快缩肌，而其他慢特异性肌肉基因，包括smyhc1，异位表达，只有一个子集的快缩肌纤维。sox6突变快缩纤维中的钙瞬变在野生型慢缩和快缩纤维的速度和幅度之间是中间的。SOX 6纯合子存活至成年期，并表现出持续的TNNC 1B错误表达以及较小的慢收缩纤维。他们的脊柱也有明显的弯曲。Sox 6转录因子是斑马鱼快速收缩肌纤维分化的关键调节因子，其作用类似于其小鼠直系同源物。本文的在线版本（doi：10.1186/s13395 - 014 - 0026 - 2）包含补充材料，可供授权用户使用。
The transcription factor Sox6 has been implicated in regulating muscle fiber type-specific gene expression in mammals. In zebrafish, loss of function of the transcription factor Prdm1a results in a slow to fast-twitch fiber type transformation presaged by ectopic expression of sox6 in slow-twitch progenitors. Morpholino-mediated Sox6 knockdown can suppress this transformation but causes ectopic expression of only one of three slow-twitch specific genes assayed. Here, we use gain and loss of function analysis to analyse further the role of Sox6 in zebrafish muscle fiber type specification. The GAL4 binary misexpression system was used to express Sox6 ectopically in zebrafish embryos. Cis-regulatory elements were characterized using transgenic fish. Zinc finger nuclease mediated targeted mutagenesis was used to analyse the effects of loss of Sox6 function in embryonic, larval and adult zebrafish. Zebrafish transgenic for the GCaMP3 Calcium reporter were used to assay Ca2+ transients in wild-type and mutant muscle fibres. Ectopic Sox6 expression is sufficient to downregulate slow-twitch specific gene expression in zebrafish embryos. Cis-regulatory elements upstream of the slow myosin heavy chain 1 (smyhc1) and slow troponin c (tnnc1b) genes contain putative Sox6 binding sites required for repression of the former but not the latter. Embryos homozygous for sox6 null alleles expressed tnnc1b throughout the fast-twitch muscle whereas other slow-specific muscle genes, including smyhc1, were expressed ectopically in only a subset of fast-twitch fibers. Ca2+ transients in sox6 mutant fast-twitch fibers were intermediate in their speed and amplitude between those of wild-type slow- and fast-twitch fibers. sox6 homozygotes survived to adulthood and exhibited continued misexpression of tnnc1b as well as smaller slow-twitch fibers. They also exhibited a striking curvature of the spine. The Sox6 transcription factor is a key regulator of fast-twitch muscle fiber differentiation in the zebrafish, a role similar to that ascribed to its murine ortholog. The online version of this article (doi:10.1186/s13395-014-0026-2) contains supplementary material, which is available to authorized users.
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影响因子：
2.7
作者：
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通讯作者：
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