DSCAM and DSCAML1 Function in Self-Avoidance in Multiple Cell Types in the Developing Mouse Retina

Abstract

DSCAM and DSCAM-LIKE1 (DSCAML1) serve diverse neurodevelopmental functions, including axon guidance, synaptic adhesion, and self-avoidance, depending on the species, cell type, and gene family member studied. We examined the function of DSCAM and DSCAML1 in the developing mouse retina. In addition to a subset of amacrine cells, Dscam was expressed in most retinal ganglion cells (RGCs). RGCs had fasciculated dendrites and clumped cell bodies in Dscam−/− mice, suggesting a role in self-avoidance. Dscaml1 was expressed in the rod circuit, and mice lacking Dscaml1 had fasciculated rod bipolar cell dendrites and clumped AII amacrine cell bodies, also indicating a role in self-avoidance. Neurons in Dscam or Dscaml1 mutant retinas stratified their processes appropriately in synaptic laminae in the inner plexiform layer, and functional synapses formed in the rod circuit in mice lacking Dscaml1. Therefore, DSCAM and DSCAML1 function similarly in self-avoidance, and are not essential for synaptic specificity in the mouse retina.

NMDA-Mediated Regulation ofDSCAMDendritic Local Translation Is Lost in a Mouse Model of Down's Syndrome

“…Although the mammalian DSCAM gene is unable to generate such wide molecular diversity, it has been demonstrated to mediate homophilic repulsion, promoting dendrite self-avoidance in the developing mouse retina (Fuerst et al, 2008(Fuerst et al, , 2009. Moreover, roles of DSCAM in both de novo and learning-related synaptogenesis have been shown using diverse biological models (Yamagata and Sanes, 2008;Li et al, 2009), and the interaction of DSCAM with PSD-95 and MAGI scaffolding proteins seems to be necessary for its synaptic function (Yamagata and Sanes, 2010).…”

“…DSCAM has been recently shown to be involved in dendrite morphogenesis in mouse retina (Fuerst et al, 2008(Fuerst et al, , 2009. To assess the impact of DSCAM overexpression on dendrite morphology of hippocampal neurons, we decided to transfect DIV7 neurons with a plasmid encoding DSCAM-IRES-GFP (Yamagata and Sanes, 2008), and to analyze the dendritic phenotype 2 d later (DIV7 ϩ 2).…”

“…Potential candidates include several HSA21 genes known to be involved in dendrite morphogenesis. Among them, Down's syndrome cell adhesion molecule (DSCAM ) has been shown to participate in dendritic tiling and self-avoidance in the mouse visual system (Fuerst et al, 2008(Fuerst et al, , 2009, two fundamental phenomena related to the formation of neural circuits. DSCAM is strongly expressed during brain development, and although it is downregulated in the adult, it persists in brain areas with high levels of synaptic plasticity, including the cortex, hippocampus, and cerebellum (Agarwala et al, 2001;Barlow et al, 2001).…”

Kirrel3 is required for the coalescence of vomeronasal sensory neuron axons into glomeruli and for male-male aggression

“…For example, Kirrel3 may regulate the self-avoidance of subsets of axons, by masking intrinsic adhesion proteins, so that they can disperse into multiple smaller glomeruli in the AOB. The transmembrane molecules DSCAM and DSCAML1 have been proposed to promote self-avoidance through such a mechanism in the mouse retina (Fuerst et al, 2009). …”

Down Syndrome Cell Adhesion Molecule (DSCAM) Associates with Uncoordinated-5C (UNC5C) in Netrin-1-mediated Growth Cone Collapse

“…While the vertebrate DSCAM gene does not encode multiple isoforms, it shares functional similarities to fly Dscam. In DSCAM deficient mice, retinal ganglion cells have defects in neuronal spacing and dendritic arborization patterns exhibiting neuronal self-avoidance phenotypes (35,36). In contrast, studies in the chicken retina have shown that DSCAM plays a role in synapse formation by promoting the targeting of retinal ganglion cell dendrites and bipolar cell axons to the same layer (37).…”