Gamma protocadherins are required for survival of spinal interneurons
Gamma protocadherins are required for survival of spinal interneurons
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DOI：
10.1016/s0896-6273(02)01090-5
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发表时间：
2002-12-05
期刊：
影响因子：
16.2
通讯作者：
Sanes, JR
中科院分区：
文献类型：
--
作者：
Wang, XZ;Weiner, JA;Sanes, JR
小鼠基因组中含有70个原钙粘蛋白（Protocadherin，Pcdh）基因。许多在神经系统中表达，表明Pcdhs可能指定神经元连接。在这里，我们分析了Pcdh-γ簇的22个连续基因。单个神经元表达Pcdh-γ基因的子集。pcdh-γ蛋白存在于大多数神经元中，并与突触相关，但不限于突触。神经元迁移、轴突生长和突触形成的早期步骤在缺乏所有22个Pcdh-γ基因的突变小鼠中进行。然而，在胚胎晚期，剧烈的神经变性会导致新生儿死亡。在突变的脊髓中，许多中间神经元丢失，但感觉和运动神经元相对幸免。在突变脊髓的培养物中，神经元分化并形成突触，但随后死亡。因此，Pcdh-γ基因至少在某些方面的连接性是必需的，但需要特定的神经元类型的生存。
The murine genome contains similar to70 protocadherin (Pcdh) genes. Many are expressed in the nervous system, suggesting that Pcdhs may specify neuronal connectivity. Here, we analyze the 22 contiguous genes of the Pcdh-gamma cluster. Individual neurons express subsets of Pcdh-gamma genes. Pcdh-gamma proteins are present in most neurons and associated with, but not confined to, synapses. Early steps in neuronal migration, axon outgrowth, and synapse formation proceed in mutant mice lacking all 22 Pcdh-gamma genes. At late embryonic stages, however, dramatic neurodegeneration leads to neonatal death. In mutant spinal cord, many interneurons are lost, but sensory and motor neurons are relatively spared. In cultures from mutant spinal cord, neurons differentiate and form synapses but then die. Thus, Pcdh-gamma genes are dispensable for at least some aspects of connectivity but required for survival of specific neuronal types.