UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans
UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans
复制标题
DOI：
10.1101/gad.13.21.2774
复制
发表时间：
1999-11-01
影响因子：
10.5
通讯作者：
Miller, DM
中科院分区：
文献类型：
--
作者：
Winnier, AR;Meir, JYJ;Miller, DM
UNC-4 同源蛋白和 Groucho 样辅阻遏物 UNC-37 指定秀丽隐杆线虫运动神经元回路中的突触选择。在unc-4突变体中，VA运动神经元与通常为其直系姐妹VB运动神经元保留的中间神经元的输入错误连接。在这里，我们展示了 UNC-4 和 UNC-37 在 VA 运动神经元中共同发挥作用，抑制 VB 特异性基因，并且这种活性取决于 UNC-37 和 UNC-4 中保守的 Engrailed 样抑制域 (ehl) 之间的物理接触。 UNC-4 ehl 结构域中的错义突变破坏了 UNC-4 和 UNC-37 之间的相互作用，并导致体内 UNC-4 依赖性阻遏蛋白活性的丧失。 UNC-37 中的补偿性氨基酸取代通过恢复与 UNC-4 的物理相互作用以及 UNC-4 依赖性的 VB 特异性基因抑制来抑制特定的 unc-4 等位基因。我们认为 UNC-4 和 UNC-37 对 VB 特异性基因的抑制对于 VA 运动神经元的野生型输入的创建是必要的。 UNC-4 和 UNC-37 的哺乳动物同源物的存在表明类似的机制可以调节脊椎动物脊髓中的突触选择。
The UNC-4 homeoprotein and the Groucho-like corepressor UNC-37 specify synaptic choice in the Caenorhabditis elegans motor neuron circuit. In unc-4 mutants, VA motor neurons are miswired with inputs from interneurons normally reserved for their lineal sisters, the VB motor neurons. Here we show that UNC-4 and UNC-37 function together in VA motor neurons to repress VB-specific genes and that this activity depends on physical contact between UNC-37 and a conserved Engrailed-like repressor domain (ehl) in UNC-4. Missense mutations in the UNC-4 ehl domain disrupt interactions between UNC-4 and UNC-37 and result in the loss of UNC-4-dependent repressor activity in vivo. A compensatory amino acid substitution in UNC-37 suppresses specific unc-4 alleles by restoring physical interactions with UNC-4 as well as UNC-4-dependent repression of VB-specific genes. We propose that repression of VB-specific genes by UNC-4 and UNC-37 is necessary for the creation of wild-type inputs to VA motor neurons. The existence of mammalian homologs of UNC-4 and UNC-37 indicates that a similar mechanism could regulate synaptic choice in the vertebrate spinal cord.