A role for axon-glial interactions and Netrin-G1 signaling in the formation of low-threshold mechanoreceptor end organs.
A role for axon-glial interactions and Netrin-G1 signaling in the formation of low-threshold mechanoreceptor end organs.
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DOI：
10.1073/pnas.2210421119
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发表时间：
2022-10-25
影响因子：
11.1
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中科院分区：
文献类型：
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我们的触觉对于从物体识别到社会交换的基本任务至关重要。然而，触摸仍然是发育水平上最不了解的感觉之一。在这里，我们研究形成的披针形复合体，这是机械感觉的最终器官与毛囊。支配多毛皮肤的触觉感觉神经元的轴突在胚胎晚期和新生儿时期延伸到皮肤中，在出生后早期发育期间修剪过多的分支，并在形成披针形复合体期间与称为末端施旺细胞（TSC）的非髓鞘化胶质细胞密切相关。此外，NGL-1及其受体Netrin-G1介导新生TSC和感觉神经元轴突末梢之间的分子对话，以促进有毛和无毛皮肤中的机械感觉末端器官形成。低阈值机械感受器（LTMR）及其皮肤终末器官将作用于皮肤的轻微机械力转化为传播到中枢神经系统的电信号。在小鼠有毛皮肤中，毛囊相关的纵向披针形复合物，其是包含与末端雪旺细胞（TSC）过程密切相关的LTMR轴突末梢的末端器官，介导对毛发偏转和皮肤凹陷的LTMR反应。在这里，我们描述了导致Aβ快速适应（RA）-LTMR和Aδ-LTMR披针形复合物形成的发育步骤。在出生后早期发育过程中，Aβ RA-LTMR和Aδ-LTMR延伸并修剪皮肤轴突分支，与新生TSC过程密切相关。Netrin-G1在这些发育中的Aβ RA-LTMR和Aδ-LTMR披针形末梢中表达，Ntng 1消融实验表明Netrin-G1在感觉神经元中起作用，以促进毛囊周围的披针形末梢的加工。由Lrrc 4c编码的Netrin-G配体（NGL-1）在TSC中表达，Lrrc 4c的消融部分表型模仿了Ntng 1突变体中观察到的披针形复合物缺陷。此外，NGL-1-Netrin-G1信号传导是不同组织类型中LTMR终末器官形成的一般介质，这一点通过与迈斯纳小体和帕西尼小体相关的Aβ RA-LTMR终末在Ntng 1和Lrrc 4c突变小鼠中也受到损害的事实得到证明。因此，部分由NGL-1-Netrin-G1信号传导介导的轴突-神经胶质相互作用促进LTMR终末器官形成。
Our sense of touch is essential for fundamental tasks ranging from object recognition to social exchange. Yet, touch remains one of the least understood senses at the developmental level. Here, we investigate the formation of lanceolate complexes, which are mechanosensory end organs associated with hair follicles. The axons of touch sensory neurons innervating hairy skin extend into the skin at late embryonic and neonatal times, prune excessive branches during early postnatal development, and closely associate with nonmyelinating glial cells, called terminal Schwann cells (TSCs) during formation of lanceolate complexes. Moreover, NGL-1 and its receptor Netrin-G1 mediate a molecular dialogue between nascent TSCs and sensory neuron axonal endings to promote mechanosensory end organ formation in both hairy and nonhairy skin. Low-threshold mechanoreceptors (LTMRs) and their cutaneous end organs convert light mechanical forces acting on the skin into electrical signals that propagate to the central nervous system. In mouse hairy skin, hair follicle–associated longitudinal lanceolate complexes, which are end organs comprising LTMR axonal endings that intimately associate with terminal Schwann cell (TSC) processes, mediate LTMR responses to hair deflection and skin indentation. Here, we characterized developmental steps leading to the formation of Aβ rapidly adapting (RA)-LTMR and Aδ-LTMR lanceolate complexes. During early postnatal development, Aβ RA-LTMRs and Aδ-LTMRs extend and prune cutaneous axonal branches in close association with nascent TSC processes. Netrin-G1 is expressed in these developing Aβ RA-LTMR and Aδ-LTMR lanceolate endings, and Ntng1 ablation experiments indicate that Netrin-G1 functions in sensory neurons to promote lanceolate ending elaboration around hair follicles. The Netrin-G ligand (NGL-1), encoded by Lrrc4c, is expressed in TSCs, and ablation of Lrrc4c partially phenocopied the lanceolate complex deficits observed in Ntng1 mutants. Moreover, NGL-1–Netrin-G1 signaling is a general mediator of LTMR end organ formation across diverse tissue types demonstrated by the fact that Aβ RA-LTMR endings associated with Meissner corpuscles and Pacinian corpuscles are also compromised in the Ntng1 and Lrrc4c mutant mice. Thus, axon–glia interactions, mediated in part by NGL-1–Netrin-G1 signaling, promote LTMR end organ formation.
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影响因子：
64.5
作者：
Li L;Rutlin M;Abraira VE;Cassidy C;Kus L;Gong S;Jankowski MP;Luo W;Heintz N;Koerber HR;Woodbury CJ;Ginty DD
通讯作者：
Ginty DD
影响因子：
25
作者：
Kim, Seho;Burette, Alain;Kim, Eunjoon
通讯作者：
Kim, Eunjoon
影响因子：
10.6
作者：
Aoki-Suzuki, M;Yamada, K;Yoshikawa, T
通讯作者：
Yoshikawa, T
影响因子：
5.2
作者：
Borg, I;Freude, K;Kalscheuer, VM
通讯作者：
Kalscheuer, VM
影响因子：
1.5
作者：
Doerflinger, NH;Macklin, WB;Popko, B
通讯作者：
Popko, B