School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
Mech Dev. 2009 Oct;126(10):852-62. doi: 10.1016/j.mod.2009.07.006. Epub 2009 Jul 28.
Klhl31 is an orthologue of Drosophila Kelch and belongs to a family of Kelch-like proteins in vertebrates. Members of this family contain multiple protein domains, including an amino-terminal broad complex/tram-track/bric-a-brac (BTB) or poxvirus and zinc finger (POZ) domain, carboxy-terminal Kelch repeats and a central linker region. We show that Klhl31 is highly expressed in the developing heart, the somite myotome and later in differentiated skeletal muscle and the myocardium. In developing somites expression of Klhl31 was initiated in the epaxial domain of the myotome, shortly after the skeletal muscle specific bHLH transcription factor, MyoD, was first expressed. Klhl31 remained expressed in skeletal muscle throughout embryonic and fetal development. Tissue ablations and rescue experiments that regulate myogenesis also govern expression of Klhl31 expression in somites. In particular, axial tissues, neural tube, floor plate and notochord, and surface ectoderm, provide combinatorial cues for myogenesis and the appropriate expression of Klhl31. We show that a combination of myogenic signals, Shh and either Wnt-1 or Wnt-6, are sufficient for Klhl31 expression in the dorsal somite. Furthermore, ectopic expression of Myf-5 led to expression of Klhl31 in the developing neural tube, indicating that Klhl31 is a novel and integral part of vertebrate myogenesis.
Klhl31 是果蝇 Kelch 的同源物,属于脊椎动物 Kelch 样蛋白家族的一员。该家族的成员包含多个蛋白结构域,包括氨基末端广泛复杂/轨道/ bric-a-brac(BTB)或痘病毒和锌指(POZ)结构域、羧基末端 Kelch 重复序列和中央连接区。我们表明,Klhl31 在发育中的心脏、体节生肌节中高度表达,随后在分化的骨骼肌和心肌中表达。在发育中的体节中,Klhl31 的表达在生肌节的轴旁域中开始,在骨骼肌特异性 bHLH 转录因子 MyoD 首次表达后不久。Klhl31 在胚胎和胎儿发育过程中一直表达在骨骼肌中。组织消融和调节生肌的拯救实验也控制着体节中 Klhl31 表达。特别是,轴性组织、神经管、基板和脊索以及表面外胚层为生肌和 Klhl31 的适当表达提供了组合线索。我们表明,肌生成信号 Shh 与 Wnt-1 或 Wnt-6 的组合足以在背侧体节中表达 Klhl31。此外,Myf-5 的异位表达导致发育中的神经管中 Klhl31 的表达,表明 Klhl31 是脊椎动物生肌的一个新的、不可或缺的组成部分。