A dynamic regulation of GDNF-family receptors correlates with a specific trophic dependency of cranial motor neuron subpopulations during development
A dynamic regulation of GDNF-family receptors correlates with a specific trophic dependency of cranial motor neuron subpopulations during development
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DOI：
10.1046/j.1460-9568.2000.00924.x
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发表时间：
2000-02-01
影响因子：
3.4
通讯作者：
Ernfors, P
中科院分区：
文献类型：
--
作者：
Mikaels, Å;Livet, J;Ernfors, P
胶质细胞源性神经营养因子 (GDNF) 家族配体可促进体内和体外发育中的运动神经元的存活。然而，并非所有神经元都能在培养物中与任何单一配体一起存活，并且 GDNF 缺失突变小鼠仅表现出部分运动神经元损失。一个有趣的可能性是，基于其功能和/或肌位组织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，因此我们通过检查发育期间和成人颅运动核亚群中 GDNF 家族受体 (gfr) 的表达来解决这个问题。我们还进一步研究了 GDNF 对颅运动神经元亚群的体内作用。共享的 ret 受体在所有检查的体细胞、鳃和内脏颅胚胎运动核中表达，表明它们在发育过程中都有能力对 GDNF 家族配体做出反应。在发育早期阶段，GDNF 受体 gfr α 1 和神经营养因子 (NTN) 受体 gfr α 2 在动眼神经、面部和脊髓附件中表达，仅 gfr α 1 在滑车、上唾液神经、三叉神经、舌下神经以及迷走神经和疑核的背运动核中表达较弱。外展核的 gfr α 1 和 gfr α 2 均为阴性。artemin (ART) 受体 gfr α 3 仅在上唾液核中表达。在面部和三叉神经核中观察到 gfr α 1 和 gfr α 2 的运动神经元亚核特异性表达，这与它们在无效突变小鼠中对 GDNF 的依赖性相对应。我们发现这些细胞核中的表达是动态的，这可能反映了它们营养因子依赖性的发育变化。对GDNF无效突变小鼠的分析表明，动态受体表达受体内配体调节，表明依赖性变化的获得可能是配体诱导的。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。
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, gfr alpha 1, and the neurturin (NTN) receptor, gfr alpha 2, were expressed in the oculomotor, facial and spinal accessory, and only gfr alpha 1 in the trochlear, superior salivatory, trigeminal, hypoglossal and weakly in the dorsal motor nucleus of the vagus and the ambiguus nucleus. The abducens nucleus was negative for both gfr alpha 1 and gfr alpha 2. The artemin (ART) receptor, gfr alpha 3, was expressed only in the superior salivatory nucleus. A motor neuron subnuclei-specific expression of gfr alpha 1 and gfr alpha 2 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 acquirement of changes in dependency could be ligand induced. Our results indicate that specific GDNF family ligands support selective muscle-motor neuron circuits during development.