LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions
LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions
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DOI：
10.1016/s0092-8674(02)00823-1
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发表时间：
2002-07-26
期刊：
影响因子：
64.5
通讯作者：
Pfaff, SL
中科院分区：
文献类型：
--
作者：
Thaler, JP;Lee, SK;Pfaff, SL
LIM同源结构域编码调控许多细胞类型的发育，尽管对这些因子如何以细胞特异性方式控制基因表达知之甚少。Lhx3参与产生两种相邻但不同的运动细胞类型，运动神经元和V2中间神经元。使用体内功能和蛋白质相互作用测定，我们发现Lhx3直接与LIM辅因子NLI结合以触发V2中间神经元分化。然而，在运动神经元中，IsI1可竞争与NLI结合，将Lhx3置换到IsI1的C末端区域上的高亲和力结合位点，从而将Lhx3从中间神经元促进因子转化为运动神经元促进因子。这种转换机制使特定的LIM复合物能够在每种细胞类型中形成，并确保神经元的命运被紧密隔离。
LIM homeodomain codes regulate the development of many cell types, though it is poorly understood how these factors control gene expression in a cell-specific manner. Lhx3 is involved in the generation of two adjacent, but distinct, cell types for locomotion, motor neurons and V2 interneurons. Using in vivo function and protein interaction assays, we found that Lhx3 binds directly to the LIM cofactor NLI to trigger V2 interneuron differentiation. In motor neurons, however, IsI1 is available to compete for binding to NLI, displacing Lhx3 to a high-affinity binding site on the C-terminal region of IsI1 and thereby transforming Lhx3 from an interneuron-promoting factor to a motor neuron-promoting factor. This switching mechanism enables specific LIM complexes to form in each cell type and ensures that neuronal fates are tightly segregated.