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A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life

机译:终端选择器可防止Hox转录开关以终生保护运动神经元身份

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摘要

To become and remain functional, individual neuron types must select during development and maintain throughout life their distinct terminal identity features, such as expression of specific neurotransmitter receptors, ion channels and neuropeptides. Here, we report a molecular mechanism that enables cholinergic motor neurons (MNs) in the ventral nerve cord to select and maintain their unique terminal identity. This mechanism relies on the dual function of the conserved terminal selector UNC-3 (Collier/Ebf). UNC-3 synergizes with LIN-39 (Scr/Dfd/Hox4-5) to directly co-activate multiple terminal identity traits specific to cholinergic MNs, but also antagonizes LIN-39’s ability to activate terminal features of alternative neuronal identities. Loss of causes a switch in the transcriptional targets of LIN-39, thereby alternative, not cholinergic MN-specific, terminal features become activated and locomotion defects occur. The strategy of a terminal selector preventing a transcriptional switch may constitute a general principle for safeguarding neuronal identity throughout life.
机译:为了成为并保持功能,单个神经元类型必须在发育过程中进行选择,并在一生中保持其独特的末端身份特征,例如特定神经递质受体,离子通道和神经肽的表达。在这里,我们报告了一种分子机制,可使腹神经索中的胆碱能运动神经元(MNs)选择并保持其独特的末端身份。此机制依赖于保守的终端选择器UNC-3(Collier / Ebf)的双重功能。 UNC-3与LIN-39(Scr / Dfd / Hox4-5)协同作用,以直接共激活胆碱能性MN特有的多个末端身份特征,但也拮抗LIN-39激活其他神经元身份的末端特征的能力。丢失原因会导致LIN-39转录靶点的转换,从而激活非胆碱能的MN特异性替代末端功能,并发生运动缺陷。末端选择子防止转录开关的策略可能构成了终生维护神经元身份的一般原则。

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