title: Muscle- and Skin-Derived Cues Jointly Orchestrate Patterning of Somatosensory Dendrites.
abstract: 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.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Díaz-Balzac
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Maisha
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: María I
authors.initials: MI
authors.lastname: Lázaro-Peña
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Lourdes A
authors.initials: LA
authors.lastname: Martin Hernandez
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Salzberg
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Aguirre-Chen
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Zaven
authors.initials: Z
authors.lastname: Kaprielian
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Electronic address: hannes.buelow@einstein.yu.edu.
authors.forename: Hannes E
authors.initials: HE
authors.lastname: Bülow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002630:Chemotactic Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003463:Cues; D003712:Dendrites / Q000502:physiology; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D009132:Muscles / Q000378:metabolism; D016415:Sequence Alignment; D012867:Skin / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002630:Chemotactic Factors; C000625700:LECT-2 protein, C elegans