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首页> 外文期刊>The European Journal of Neuroscience >A dynamic regulation of GDNF-family receptors correlates with a specific trophic dependency of cranial motor neuron subpopulations during development.
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A dynamic regulation of GDNF-family receptors correlates with a specific trophic dependency of cranial motor neuron subpopulations during development.

机译:GDNF-家族受体的动态调节与发育过程中颅运动神经元亚群的特定营养依赖性相关。

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Glial cell line-derived neurotrophic factor (GDNF) family ligands promote the survival of developing motor neurons in vivo and in vitro. However, not all neurons survive with any single ligand in culture and GDNF null mutant mice display only a partial motor neuron loss. An interesting possibility is that subpopulations of motor neurons based on their function and/or their myotopic organization require distinct members of GDNF family ligands. Because responsiveness to the different ligands depends on the expression of their cognate ligand-binding receptor we have herein addressed this issue by examining the expression of GDNF-family receptors (gfr) during development and in the adult in cranial motor nuclei subpopulations. We have furthermore examined the in vivo role of GDNF for cranial motor neuron subpopulations. The shared ret receptor was expressed in all somatic, branchial and visceral cranial embryonic motor nuclei examined, showing that they are all competent to respond to GDNF family ligands during development. At early stages of development both the GDNF receptor, gfralpha1, and the neurturin (NTN) receptor, gfralpha2, were expressed in the oculomotor, facial and spinal accessory, and only gfralpha1 in the trochlear, superior salivatory, trigeminal, hypoglossal and weakly in the dorsal motor nucleus of the vagus and the ambiguous nucleus. The abducens nucleus was negative for both gfralpha1 and gfralpha2. The artemin (ART) receptor, gfralpha3, was expressed only in the superior salivatory nucleus. A motor neuron subnuclei-specific expression of gfralpha1 and gfralpha2 was seen in the facial and trigeminal nuclei which corresponded to their dependence on GDNF in null mutant mice. We found that the expression was dynamic in these nuclei, which may reflect developmental changes in their trophic factor dependency. Analysis of GDNF null mutant mice revealed that the dynamic receptor expression is regulated by the ligand in vivo, indicating that the attainment of changes in dependency could be ligand induced. Our results indicate that specific GDNF family ligands support selective muscle-motor neuron circuits during development.
机译:胶质细胞源性神经营养因子(GDNF)家族配体在体内和体外促进发育中的运动神经元的存活。但是,并不是所有的神经元都能在培养物中使用任何单一配体存活,并且GDNF空突变小鼠仅表现出部分运动神经元丢失。一个有趣的可能性是,基于运动神经元的功能和/或肌组织组成的运动神经元亚群需要GDNF家族配体的不同成员。由于对不同配体的反应性取决于其同源配体结合受体的表达,因此我们在本文中通过检查发育过程中和成年颅脑运动核亚群中GDNF家族受体(gfr)的表达来解决此问题。我们进一步检查了GDNF在颅内运动神经元亚群中的体内作用。共享的ret受体在所有体细胞,分支和内脏颅内胚胎运动核中都有表达,表明它们都具有在发育过程中对GDNF家族配体做出反应的能力。在发育的早期阶段,GDNF受体gfralpha1和神经营养素(NTN)受体gfralpha2在动眼,面部和脊柱附件中表达,仅gfralpha1在滑车,上唾液腺,三叉神经,舌下神经和微弱的滑膜中表达。迷走神经的背运动核和模棱两可的核。 gfralpha1和gfralpha2的外展核均阴性。青蒿素(ART)受体gfralpha3仅在唾液上核中表达。在面部和三叉神经核中发现了gfralpha1和gfralpha2的运动神经元亚核特异性表达,这与其在无效突变小鼠中对GDNF的依赖性相对应。我们发现这些核中的表达是动态的,这可能反映了其营养因子依赖性的发展变化。 GDNF null突变小鼠的分析表明,动态受体的表达受体内配体的调节,表明依赖性变化的实现可能是配体诱导的。我们的结果表明,特定的GDNF家族配体在发育过程中支持选择性的肌肉运动神经元回路。

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