A SERIES OF MUTATIONS IN THE D-MEF2 TRANSCRIPTION FACTOR REVEAL MULTIPLE FUNCTIONS IN LARVAL AND ADULT MYOGENESIS IN DROSOPHILA

A SERIES OF MUTATIONS IN THE D-MEF2 TRANSCRIPTION FACTOR REVEAL MULTIPLE FUNCTIONS IN LARVAL AND ADULT MYOGENESIS IN DROSOPHILA
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DOI:
10.1006/dbio.1995.1269
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发表时间:
1995-09-01
影响因子:
2.7
通讯作者:
SCHULZ, RA
SCHULZ, RA
中科院分区:
生物学3区
文献类型:
--
作者:
RANGANAYAKULU, G;ZHAO, B;SCHULZ, RA

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D-mef 2基因编码MADS结构域转录因子,在果蝇胚胎分化的肌肉及其前体中表达。由于上游转录控制序列的缺失,D-MEF 2蛋白缺陷的胚胎不能形成肌肉,这表明该基因是肌肉细胞分化所必需的。为了直接证明D-mef 2在胚胎肌肉发生中的作用,我们分离了含有EMS诱导的点突变的基因突变体,表征了这些突变对D-mef 2蛋白稳定性和核定位的影响,并分析了由此产生的肌肉表型。我们的研究结果表明,在躯体肌肉谱系中,D-mef 2是体壁肌肉的形成和图案化所必需的。在没有体细胞肌发生的情况下,成肌细胞群中存在广泛的凋亡。相反,在心肌谱系中,背血管的形态发生正常,但三个肌球蛋白亚基基因不表达。突变胚胎还表现出异常的中肠形态,这与α(PS2)整合素基因表达和肌肉特异性增强子功能的缺乏相关,表明D-mef 2调节编码该整合素亚基的膨胀位点。D-MEF 2也表达于脂肪上皮细胞中,并且罕见的D-mef 2转杂合子突变体成年人不能产生ny,这与在间接飞行肌中观察到的缺陷一致。这些结果表明,D-mef 2基因在果蝇发育过程中的肌肉发生和组织形态发生中具有多种功能。(C)出版社:Academic Press
The D-mef2 gene encodes a MADS domain transcription factor expressed in differentiated muscles and their precursors in the Drosophila embryo. Embryos deficient for D-MEF2 protein due to a deletion of upstream transcriptional control sequences fail to form muscle, suggesting that the gene is required for muscle cell differentiation. To directly demonstrate a role for D-mef2 in embryonic myogenesis, we isolated gene mutants containing EMS-induced point mutations, characterized the effects of these mutations on D-MEF2 protein stability and nuclear localization, and analyzed the resulting muscle phenotypes. Our results show that in the somatic muscle lineage, D-mef2 is required for both the formation and patterning of body wall muscle. In the absence of somatic myogenesis, there is extensive apoptosis among the myoblast cell population. In contrast, in the cardiac muscle lineage, morphogenesis of the dorsal vessel occurs normally but the three myosin subunit genes are not expressed. Mutant embryos also exhibit an abnormal midgut morphology, which correlates with the absence of alpha(PS2) integrin gene expression and muscle-specific enhancer function, suggesting that D-mef2 regulates the inflated locus which encodes this integrin subunit. D-MEF2 is also expressed in adepithelial cells and rare D-mef2 transheterozygous mutant adults fail to ny, consistent with defects observed in the indirect flight muscles. These results demonstrate that the D-mef2 gene has multiple functions in myogenesis and tissue morphogenesis during Drosophila development. (C) 1995 Academic Press, Inc.