Lineage-based primary muscle fiber type diversification independent of MEF2 and NFAT in chick embryos.
Lineage-based primary muscle fiber type diversification independent of MEF2 and NFAT in chick embryos.
复制标题
鸡胚中基于谱系的初级肌纤维类型多样化独立于 MEF2 和 NFAT。
DOI：
10.1007/s10974-011-9242-0
复制
发表时间：
2011
影响因子：
2.7
通讯作者：
DiMario,JosephX
中科院分区：
文献类型：
--
作者：
Theobald,Jillian;DiMario,JosephX
主要的鸟类骨骼肌纤维类型的差异是基于成肌细胞谱系和独立的神经支配。为了理解这种肌发生模式的基础，专门致力于形成快速或快速/缓慢肌纤维类型的胚胎成肌细胞被分离，表征，并检查其转录调节慢肌球蛋白重链2（MyHC 2）基因的能力。肌源性基本螺旋-环-螺旋蛋白结合位点内的慢MyHC 2启动子突变，并没有直接快速与快速/缓慢肌纤维类型的发展。使用启动子分析结合过表达研究和转录传感器，确定活化T细胞核因子（NFATc 1）和MEF 2A在慢MyHC 2基因调控中的作用。MEF 2A在快和快/慢初级肌纤维中激活慢MyHC 2启动子。相反，NFATc 1抑制启动子活性。这些结果不支持MEF 2和NFAT作为初级肌纤维类型差异的直接调节因子的作用。相反，这些结果反映了慢MyHC 2基因在初级肌纤维类型中调节模式的内在差异。
Differences in primary avian skeletal muscle fiber types are based on myoblast cell lineages and independent of innervation. To understand the basis for this mode of myogenesis, embryonic myoblasts specifically committed to the formation of either fast or fast/slow muscle fiber types were isolated, characterized, and examined for their capacities to transcriptionally regulate the slow myosin heavy chain 2 (MyHC2) gene. Myogenic basic helix-loop-helix protein binding sites within the slow MyHC2 promoter were mutated and did not direct fast versus fast/slow muscle fiber type development. Using promoter analyses coupled with overexpression studies and transcriptional sensors, the roles of Nuclear Factor of Activated T cells (NFATc1), and MEF2A in regulation of the slow MyHC2 gene were determined. MEF2A activated the slow MyHC2 promoter in both fast and fast/slow primary muscle fibers. In contrast, NFATc1 repressed promoter activity. These results do not support the roles of MEF2 and NFAT as direct regulators of primary muscle fiber type differences. Rather, the results reflect intrinsic differences in the modes of regulation of the slow MyHC2 gene in primary muscle fiber types.