Developmental regulation of myosin gene expression in mouse cardiac muscle.
Developmental regulation of myosin gene expression in mouse cardiac muscle.
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DOI：
10.1083/jcb.111.6.2427
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发表时间：
1990-12
期刊：
影响因子：
--
通讯作者：
Buckingham M
中科院分区：
文献类型：
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作者：
Lyons GE;Schiaffino S;Sassoon D;Barton P;Buckingham M
哺乳动物心肌肌球蛋白重链（MHC）的两种亚型MHC α和MHC β的表达在出生后受到多种刺激（包括血清激素水平）的调节。在胚胎快速生长的心肌中，调控肌球蛋白基因表达的因素尚不清楚。利用心肌中表达的两个MHC基因和两个肌球蛋白碱轻链（myosin碱轻链，MLC）基因对应的35s标记的同种型特异性cRNA探针，通过原位杂交研究了这些不同基因在发育中的小鼠心脏中的时空表达模式。在性交后7.5至8天（p.c），新形成的心管开始在整个心肌中高水平表达MHC α、MHC β、MLC1心房（MLC1A）和MLC1心室（MLC1V）基因转录物。当一个独特的心室室在8 - 9天之间形成时，MHC β mrna开始局限于心室肌细胞。这一过程在10.5 d左右完成。在此期间，心室肌细胞的MHC α mRNA水平下降，但在心房肌细胞中继续高水平表达。MHC α转录本在心室肌细胞中持续减少，直到产后16天，在低水平时可检测到，但随后增加，并最终在出生后7天取代心室肌中的MHC β mrna。与MHC β一样，MLC1V转录本也局限于心室肌细胞，但速度较慢。MLC1V mRNA在心房细胞中持续低水平检测到，直到15.5天。MLC1A mRNA水平逐渐降低，但在心室细胞中仍可检测到，直到出生后几天。这种产前小鼠心脏肌球蛋白表型变化的动态模式表明，在心脏发育过程中，肌球蛋白亚型的细胞特异性表达存在不同的调节机制。
Expression of the two isoforms of cardiac myosin heavy chain (MHC), MHC alpha and MHC beta, in mammals is regulated postnatally by a variety of stimuli, including serum hormone levels. Less is known about the factors that regulate myosin gene expression in rapidly growing cardiac muscle in embryos. Using isoform-specific 35S-labeled cRNA probes corresponding to the two MHC genes and the two myosin alkali light chain (MLC) genes expressed in cardiac muscle, we have investigated the temporal and spatial pattern of expression of these different genes in the developing mouse heart by in situ hybridization. Between 7.5 and 8 d post coitum (p.c.), the newly formed cardiac tube begins to express MHC alpha, MHC beta, MLC1 atrial (MLC1A), and MLC1 ventricular (MLC1V) gene transcripts at high levels throughout the myocardium. As a distinct ventricular chamber forms between 8 and 9 d p.c., MHC beta mRNAs begin to be restricted to ventricular myocytes. This process is complete by 10.5 d p.c. During this time, MHC alpha mRNA levels decrease in ventricular muscle cells but continue to be expressed at high levels in atrial muscle cells. MHC alpha transcripts continue to decrease in ventricular myocytes until 16 d p.c., when they are detectable at low levels, but then increase, and finally replace MHC beta mRNAs in ventricular muscle by 7 d after birth. Like MHC beta, MLC1V transcripts become restricted to ventricular myocytes, but at a slower rate. MLC1V mRNAs continue to be detected at low levels in atrial cells until 15.5 d p.c. MLC1A mRNA levels gradually decrease but are still detectable in ventricular cells until a few days after birth. This dynamic pattern of changes in the myosin phenotype in the prenatal mouse heart suggests that there are different regulatory mechanisms for cell-specific expression of myosin isoforms during cardiac development.