A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development.
A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development.
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DOI：
10.1186/1471-2164-11-378
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发表时间：
2010-06-15
期刊：
影响因子：
4.4
通讯作者：
Tellam RL
中科院分区：
文献类型：
--
作者：
Byrne K;Vuocolo T;Gondro C;White JD;Cockett NE;Hadfield T;Bidwell CA;Waddell JN;Tellam RL
晚期胎儿和新生动物之间的发育过渡与骨骼肌功能的深刻变化有关，因为它适应了运动和姿势支持对抗重力的新生理需求。支持这种适应过程的机制尚不清楚，但很可能是由激素水平的变化引发的。我们测试的假设，这种发展的转变是与大协调的骨骼肌基因转录的变化。使用绵羊模型，在三个胎儿发育时间点（胎儿发育的80、100和120 d）和两个出生后时间点（一个大约产后3天，第二个在3个月大）采集背最长肌骨骼肌进行转录谱分析。发育时间进程主要是在胎儿发育后期（120天胎儿发育）和产后1-3天之间的间隔期间，2，471个基因表达的大变化。在此期间独特上调的基因的功能分析显示，氧化代谢和三羧酸循环的强烈富集表明线粒体活性增强。对这些发育时间点组织的组织学检查直接证实了晚期胎儿和出生后早期样本之间线粒体活性的显著增加。在此胎儿到新生儿的过渡过程中上调的基因的启动子富含雌激素受体1和雌激素相关受体α顺式调节基序。在此期间下调的基因突出了一系列功能的弱化，包括Wnt信号传导、细胞粘附和分化。在这个晚期胎儿-出生后过渡之前和两个出生后时间点之间的基因表达也有变化。前者基因富集涉及细胞外基质和免疫应答的功能，而后者主要涉及与代谢过程的转录调控相关的功能。它的结论是，在骨骼肌发育后期，有大量的基因，其中许多可能是由雌激素水平的增加引发的转录的实质性和协调的变化。这些变化可能是肌肉适应出生后环境中新的生理需求的基础。
The developmental transition between the late fetus and a newborn animal is associated with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels. We tested the hypothesis that this developmental transition is associated with large coordinated changes in the transcription of skeletal muscle genes. Using an ovine model, transcriptional profiling was performed on Longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) and two postnatal time points, one approximately 3 days postpartum and a second at 3 months of age. The developmental time course was dominated by large changes in expression of 2,471 genes during the interval between late fetal development (120 d fetal development) and 1-3 days postpartum. Analysis of the functions of genes that were uniquely up-regulated in this interval showed strong enrichment for oxidative metabolism and the tricarboxylic acid cycle indicating enhanced mitochondrial activity. Histological examination of tissues from these developmental time points directly confirmed a marked increase in mitochondrial activity between the late fetal and early postnatal samples. The promoters of genes that were up-regulated during this fetal to neonatal transition were enriched for estrogen receptor 1 and estrogen related receptor alpha cis-regulatory motifs. The genes down-regulated during this interval highlighted de-emphasis of an array of functions including Wnt signaling, cell adhesion and differentiation. There were also changes in gene expression prior to this late fetal - postnatal transition and between the two postnatal time points. The former genes were enriched for functions involving the extracellular matrix and immune response while the latter principally involved functions associated with transcriptional regulation of metabolic processes. It is concluded that during late skeletal muscle development there are substantial and coordinated changes in the transcription of a large number of genes many of which are probably triggered by increased estrogen levels. These changes probably underpin the adaption of muscle to new physiological demands in the postnatal environment.
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影响因子：
2.7
作者：
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通讯作者：
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