HLH54F is required for the specification and migration of longitudinal gut muscle founders from the caudal mesoderm of Drosophila
HLH54F is required for the specification and migration of longitudinal gut muscle founders from the caudal mesoderm of Drosophila
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DOI：
10.1242/dev.046573
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发表时间：
2010-09-15
期刊：
影响因子：
4.6
通讯作者：
Frasch, Manfred
中科院分区：
文献类型：
--
作者：
Ismat, Afshan;Schaub, Christoph;Frasch, Manfred
HLH54F是果蝇的同源基因，编码脊椎动物的基本螺旋-环-螺旋结构域基因囊蛋白和肌球蛋白，表达于中肠纵肌的创始细胞和发育中的肌纤维。这些细胞从中胚层最后面的部分下来，称为尾部内脏中胚层(CVM)，在经历成肌细胞融合和肌肉纤维形成之前迁移到主干内脏中胚层。我们发现HLH54F在CVM中的表达受末端模式基因和蜗牛的组合调控。我们产生了HLH54F突变，并表明该基因对CVM细胞和纵向中肠肌创始人的规范、迁移和生存至关重要。HLH54F突变的胚胎、幼虫和成虫缺乏所有的纵向中肠肌肉，导致肠道形态和完整性的缺陷。HLH54F作为基因表达的直接激活子的功能通过我们对来自Dorocross基因座的CVM特异性增强子的分析来举例，这需要来自HLH54F和biniou的前馈输入。我们得出结论，HLH54F是CVM发育的最早的特异性调节因子，它在这个基本上不依赖扭曲的中胚层细胞群的发育和分化的所有主要方面都发挥着关键作用。
HLH54F, the Drosophila ortholog of the vertebrate basic helix-loop-helix domain-encoding genes capsulin and musculin, is expressed in the founder cells and developing muscle fibers of the longitudinal midgut muscles. These cells descend from the posterior-most portion of the mesoderm, termed the caudal visceral mesoderm (CVM), and migrate onto the trunk visceral mesoderm prior to undergoing myoblast fusion and muscle fiber formation. We show that HLH54F expression in the CVM is regulated by a combination of terminal patterning genes and snail. We generated HLH54F mutations and show that this gene is crucial for the specification, migration and survival of the CVM cells and the longitudinal midgut muscle founders. HLH54F mutant embryos, larvae, and adults lack all longitudinal midgut muscles, which causes defects in gut morphology and integrity. The function of HLH54F as a direct activator of gene expression is exemplified by our analysis of a CVM-specific enhancer from the Dorsocross locus, which requires combined inputs from HLH54F and Biniou in a feed-forward fashion. We conclude that HLH54F is the earliest specific regulator of CVM development and that it plays a pivotal role in all major aspects of development and differentiation of this largely twist-independent population of mesodermal cells.