Deng Hua, Hughes Sarah C, Bell John B, Simmonds Andrew J
Department of Cell Biology, Department of Biological Sciences, and Department of Medical Genetics, University of Alberta, Edmonton, Canada.
Mol Biol Cell. 2009 Jan;20(1):256-69. doi: 10.1091/mbc.e08-03-0288. Epub 2008 Nov 5.
Vertebrate development requires the activity of the myocyte enhancer factor 2 (mef2) gene family for muscle cell specification and subsequent differentiation. Additionally, several muscle-specific functions of MEF2 family proteins require binding additional cofactors including members of the Transcription Enhancing Factor-1 (TEF-1) and Vestigial-like protein families. In Drosophila there is a single mef2 (Dmef2) gene as well single homologues of TEF-1 and vestigial-like, scalloped (sd), and vestigial (vg), respectively. To clarify the role(s) of these factors, we examined the requirements for Vg and Sd during Drosophila muscle specification. We found that both are required for muscle differentiation as loss of sd or vg leads to a reproducible loss of a subset of either cardiac or somatic muscle cells in developing embryos. This muscle requirement for Sd or Vg is cell specific, as ubiquitous overexpression of either or both of these proteins in muscle cells has a deleterious effect on muscle differentiation. Finally, using both in vitro and in vivo binding assays, we determined that Sd, Vg, and Dmef2 can interact directly. Thus, the muscle-specific phenotypes we have associated with Vg or Sd may be a consequence of alternative binding of Vg and/or Sd to Dmef2 forming alternative protein complexes that modify Dmef2 activity.
脊椎动物的发育需要肌细胞增强因子2(mef2)基因家族的活性来进行肌肉细胞的特化及随后的分化。此外,MEF2家族蛋白的几种肌肉特异性功能需要结合其他辅助因子,包括转录增强因子-1(TEF-1)和类残翅蛋白家族的成员。在果蝇中,分别有单个mef2(Dmef2)基因以及TEF-1和类残翅蛋白的单个同源物,即缺刻(sd)和残翅(vg)。为了阐明这些因子的作用,我们研究了果蝇肌肉特化过程中对Vg和Sd的需求。我们发现两者都是肌肉分化所必需的,因为sd或vg的缺失会导致发育中胚胎的一部分心脏或体肌细胞出现可重复的缺失。对Sd或Vg的这种肌肉需求是细胞特异性的,因为在肌肉细胞中普遍过表达这两种蛋白中的任何一种或两者都会对肌肉分化产生有害影响。最后,通过体外和体内结合试验,我们确定Sd、Vg和Dmef2可以直接相互作用。因此,我们观察到的与Vg或Sd相关的肌肉特异性表型可能是Vg和/或Sd与Dmef2形成改变Dmef2活性的替代蛋白复合物的替代结合的结果。