Bao Z Z, Bruneau B G, Seidman J G, Seidman C E, Cepko C L
Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Science. 1999 Feb 19;283(5405):1161-4. doi: 10.1126/science.283.5405.1161.
The vertebrate heart consists of two types of chambers, the atria and the ventricles, which differ in their contractile and electrophysiological properties. Little is known of the molecular mechanisms by which these chambers are specified during embryogenesis. Here a chicken iroquois-related homeobox gene, Irx4, was identified that has a ventricle-restricted expression pattern at all stages of heart development. Irx4 protein was shown to regulate the chamber-specific expression of myosin isoforms by activating the expression of the ventricle myosin heavy chain-1 (VMHC1) and suppressing the expression of the atrial myosin heavy chain-1 (AMHC1) in the ventricles. Thus, Irx4 may play a critical role in establishing chamber-specific gene expression in the developing heart.
脊椎动物的心脏由两种类型的腔室组成,即心房和心室,它们在收缩和电生理特性上有所不同。关于这些腔室在胚胎发育过程中如何被特化的分子机制,我们知之甚少。在此,我们鉴定出了一个与鸡类伊洛魁族相关的同源框基因Irx4,它在心脏发育的所有阶段都具有心室特异性的表达模式。研究表明,Irx4蛋白通过激活心室肌球蛋白重链-1(VMHC1)的表达并抑制心房肌球蛋白重链-1(AMHC1)在心室中的表达,来调节肌球蛋白同工型的腔室特异性表达。因此,Irx4可能在发育中的心脏建立腔室特异性基因表达方面发挥关键作用。