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

Sensory dendrite arbors are patterned through cell-autonomously and non-cell-autonomously functioning factors [1–3]. Yet, only a few non-cell-autonomously acting proteins have been identified, including semaphorins [4, 5], brain-derived neurotrophic factors (BDNFs) [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 leucine-rich transmembrane receptor DMA-1/LRR-TM expressed 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 and 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 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. [Display omitted] •The conserved cue LECT-2/Chondromodulin II patterns somatosensory dendrite arbors•LECT-2/Chondromodulin II acts as a muscle-derived, diffusible cue•LECT-2 acts together with the conserved MNR-1/SAX-7/DMA-1 adhesion complex•LECT-2/Chondromodulin II localization is dependent on skin-derived cues Díaz-Balzac et al. show that muscle-derived LECT-2/Chondromodulin II serves as a diffusible cue to pattern sensory dendrite arbors in Caenorhabditis elegans together with a conserved skin-derived adhesion complex.