Muscle- and Skin-Derived Cues Jointly Orchestrate Patterning of Somatosensory Dendrites

Abstract

Summary Sensory dendrite arbors are patterned through cell-autonomously and non-autonomously functioning factors [1–3]. Yet, only a few non-autonomously acting proteins have been identified, including semaphorins [4, 5], brain derived neurotrophic factors (BDNF) [6], UNC-6/Netrin [7], and the conserved MNR-1/Menorin–SAX-7/L1CAM cell adhesion complex [8, 9]. This complex acts from the skin to pattern the stereotypic dendritic arbors of PVD and FLP somatosensory neurons in Caenorhabditis elegans through the dendritic leucine rich transmembrane receptor DMA-1/LRR-TM on PVD neurons [8, 9]. Here we describe a role for the diffusible C. elegans protein LECT-2, which is homologous to vertebrate leukocyte cell-derived chemotaxin 2 (LECT2)/chondromodulin II. LECT2/chondromodulin II has been implicated in a variety of pathological conditions [10–13], but the developmental functions of LECT2 have remained elusive. We find that LECT-2/Chondromodulin II is required for development of PVD and FLP dendritic arbors, and can act as a diffusible cue from a distance to shape dendritic arbors. Expressed in body wall muscles, LECT-2 decorates neuronal processes as well as hypodermal cells in a pattern similar to the cell adhesion molecule SAX-7/L1CAM. LECT-2 functions genetically downstream of the MNR-1/Menorin–SAX-7/L1CAM adhesion complex, and upstream of the DMA-1 receptor. LECT-2 localization is dependent on SAX-7/L1CAM, but not on MNR-1/Menorin or DMA-1/LRR-TM, suggesting that LECT-2 functions as part of the skin-derived MNR-1/Menorin–SAX-7/L1CAM adhesion complex. Collectively, our findings suggest that muscle-derived LECT-2/Chondromodulin II acts as a muscle-derived, diffusible cofactor together with a skin-derived cell adhesion complex to orchestrate the molecular interactions of three tissues during patterning of somatosensory dendrites.

Stress-induced dendritic branching inC. elegansrequires both common arborization effectors and stress-responsive molecular pathways

“…Finally, the muscle-secreted protein LECT-2 interacts with the DMA-1 complex to promote PVD branching (11,18). Consistent with this, we found that loss of lect-2 causes defects in dauer-specific IL2 branching that can be rescued through muscle-specific expression ( Fig.…”

“…However, we show that the DMA-1 complex is not sufficient to induce branching in the IL2s. Overexpression of DMA-1 in the IL2s during non-dauer stages did not induce branching despite the presence of SAX-7, MNR-1, and LECT-2 (9,18). Similarly, we found that during dauer the FLPs stop branching despite its expression of DMA-1.…”

“…In the PVDs, DMA-1 acts through a protein complex for proper branching (10,11,17,18). sax-7 encodes a cell adhesion molecule, homologous to mammalian L1CAM, which acts in the surrounding hypodermis to control PVD arborization (9,10).…”

Separate transcriptionally regulated pathways specify distinct classes of sister dendrites in a nociceptive neuron

“…The LRR (Leucine Rich Repeat) protein DMA-1 likely acts in the same pathway as it shows a similar mutant PVD branching defect (Dong et al, 2013; Smith et al, 2013). DMA-1 mediates dendritic outgrowth as a PVD-expressed component of a quarternary complex containing the cell surface proteins SAX-7/L1CAM and Menorin/MNR-1 in the epidermis and the soluble factor LECT-2 (Díaz-Balzac et al, 2016; Dong et al, 2013; Liang et al, 2015; O’Brien et al, 2016; Salzberg et al, 2013; Zou et al, 2016). These interactions are necessary for 3° and 4° branching, but additional epidermal cues are likely required for pioneer 2° branch outgrowth as the dma-1 mutant phenotype is more severe than that of either sax-7 , mnr-1 , or lect-2 .…”

A neuronal MAP kinase constrains growth of aC. eleganssensory dendrite throughout the life of the organism

“…While C. elegans has been used extensively as a model for axon development [11], considerably less attention has been paid to its dendrites. Most of the work has focused on interesting sensory neurons with complex branched dendrites, and has revealed mechanisms of dendritic branch formation and spacing [12][13][14][15][16][17][18][19][20][21][22][23], dendritic self-avoidance [24], and even dendrite tiling [25]. By comparison, dendrites with simple unbranched morphologies have been used as a model for understanding axon-dendrite polarity [26,27].…”