An Extracellular Adhesion Molecule Complex Patterns Dendritic Branching and Morphogenesis

Abstract

Summary Robust dendrite morphogenesis is a critical step in the development of reproducible neural circuits. However, little is known about the extracellular cues that pattern complex dendrite morphologies. In the model nematode C. elegans, the sensory neuron PVD establishes stereotypical, highly-branched dendrite morphology. Here, we report the identification of a tripartite ligand-receptor complex of membrane adhesion molecules that is both necessary and sufficient to instruct spatially restricted growth and branching of PVD dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations in the surrounding hypodermal tissue, while DMA-1 acts as the cognate receptor on PVD. Mutations in this complex lead to dramatic defects in the formation, stabilization, and organization of the dendritic arbor. Ectopic expression of SAX-7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a DMA-1 dependent manner. Both in vivo and in vitro experiments indicate that all three molecules are needed for interaction.

AFF-1 fusogen can rejuvenate the regenerative potential of adult dendritic trees via self-fusion

“…1A) (Oren-Suissa et al, 2010). These dendritic trees arise and are dynamically maintained through several intrinsic and extrinsic genetic pathways (Chatzigeorgiou et al, 2010;Cohen et al, 2014;Dong et al, 2013Dong et al, , 2015Husson et al, 2012;Liu and Shen, 2011;Maniar et al, 2012;Oren-Suissa et al, 2010;Salzberg et al, 2013;Smith et al, 2010;Wei et al, 2015).…”

A Novel Nondevelopmental Role of the SAX-7/L1CAM Cell Adhesion Molecule in Synaptic Regulation inCaenorhabditis elegans

“…The impairment of these potential roles may also account for some of the CRASH symptoms in the L1 disorder and possibly the autism and neuropsychiatric disorders that are strongly associated with L1CAMs. This study takes advantage of the ease in performing genetic modifier analyses in C. elegans to dissect the functions of the C. elegans L1CAM, SAX-7, which in addition to controlling dendritic branching morphogenesis, also maintains the position of neurons and their axons to preserve nervous system architecture (Zallen et al 1999;Sasakura et al 2005;Wang et al 2005;Dong et al 2013;Salzberg et al 2013). Here, we provide evidence demonstrating that sax-7 acts as a modifier of synaptic regulation, uncovering a novel nondevelopmental neuronal role for sax-7.…”

Transcription factors and effectors that regulate neuronal morphology

“…In its absence, dendritic arbors are greatly reduced (Liu and Shen, 2012). Two recent studies demonstrated that DMA-1 forms a complex in trans with the MNR-1 and L1CAM/SAX-7 receptors expressed in the skin, and that this complex promotes dendritic growth (Dong et al, 2013;Salzberg et al, 2013). The dma-1 phenotype is strikingly similar to the mec-3 and hpo-30 phenotypes.…”