A role for axon–glial interactions and Netrin-G1 signaling in the formation of low-threshold mechanoreceptor end organs

Abstract

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.

Developmental pruning of sensory neurites by mechanical tearing in Drosophila

“…For example, pruning of Drosophila mushroom body γ neuron axons requires phagocytic glia (Awasaki et al, 2006;Hoopfer et al, 2006), and forces caused by phagocytic engulfment could act to actively break pruning axons. Peripheral sensory neurite morphogenesis in mammals also involves pruning (Meltzer et al, 2022). It is interesting to speculate that movementinduced mechanical forces could play an important role here as well.…”

Exploration of the Core Pathways and Potential Targets of Luteolin Treatment on Late-Onset Depression Based on Cerebrospinal Fluid Proteomics

“…NTNG1 is crucial in neural development, including the promotion synapse formation, axon growth and the regulation of synaptic plasticity. Moreover, NTNG1 deficiency contributed to fear-like and anxiety-like behavioral disturbances [ 54 ].…”

Investigating the Gliogenic Genes and Signaling Pathways in the Pathogenesis of Huntington’s Disease: A Systematic Review

“…They are involved in directing the growth of axons and guiding migrating cells during neural circuit formation. Netrins interact with their receptors, known as DCC (Deleted in Colorectal Cancer) and UNC5 receptors, to mediate attractive and repulsive cues that guide developing neurons and glial cells to their appropriate locations [130]. In the context of gliogenesis, netrins and their receptors are likely to in uence the migration and differentiation of neural progenitor cells into glial cell lineages, contributing to the proper organization of neural tissue [131].…”