Drosophila Sensory Neurons Require Dscam for Dendritic Self-Avoidance and Proper Dendritic Field Organization

Soba, Peter; Zhu, Sijun; Emoto, Kazuo; Younger, Susan; Yang, Shun-Jen; Yu, Hung–Hsiang; Lee, Tzumin; Jan, Yuh Nung; Jan, Yuh-Nung

doi:10.1016/j.neuron.2007.03.029

Cited by 262 publications

(296 citation statements)

References 35 publications

Supporting

Mentioning

287

Contrasting

Order By: Relevance

“…Up to now, Dscam2 and its mouse homolog Dscam are only known cell surface transmembrane proteins to be implicated in mediating mutual repulsion for axonal/dendrite tiling (Millard et al, 2007;Fuerst et al, 2008). In addition, Dscam and the receptor tyrosine phosphatase Hm-LAR2 have been shown to be involved in mediating selfavoidance, a phenomenon referring to the avoidance of sister neurites projected from a single neuron, in sensory neurons in Drosophila (Hughes et al, 2007;Matthews et al, 2007;Soba et al, 2007) and the comb cell in Leech (Gershon et al, 1998), respectively.…”

Section: Discussionmentioning

confidence: 99%

The Conserved Ig Superfamily Member Turtle Mediates Axonal Tiling in Drosophila

Ferguson

Hong²,

Cameron³

et al. 2009

J. Neurosci.

View full text Add to dashboard Cite

Restriction of adjacent same-type axons/dendrites to separate single columns for specific neuronal connections is commonly observed in vertebrates and invertebrates, and is necessary for proper processing of sensory information. Columnar restriction is conceptually similar to tiling, a phenomenon referring to the avoidance of neurites from adjacent same-type neurons. The molecular mechanism underlying the establishment of columnar restriction or axonal/dendritic tiling remains largely undefined. Here, we identify Turtle (Tutl), a member of the conserved Tutl/Dasm1/IgSF9 subfamily of the Ig superfamily, as a key player in regulating the tiling pattern of R7 photoreceptor terminals in Drosophila. Tutl functions to prevent fusion between two adjacent R7 terminals, and acts in parallel to the Activin pathway. Tutl mediates homophilic cell-cell interactions. We propose that extrinsic terminal-terminal recognition mediated by Tutl, acts in concert with intrinsic Activin-dependent control of terminal growth, to restrict the connection made by each R7 axon to a single column.

show abstract

Section: Discussionmentioning

confidence: 99%

The Conserved Ig Superfamily Member Turtle Mediates Axonal Tiling in Drosophila

Ferguson

Hong²,

Cameron³

et al. 2009

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In insects, the DSCAM1 gene can be differentially spliced into potentially tens of thousands of isoforms (Schmucker et al 2000). The processes of a neuron expressing a particular collection of isoforms is repulsed by its own process in a DSCAM1 dependant manner, but mix freely with neuronal processes expressing disparate DSCAM1 isoforms (Hughes et al 2007;Matthews et al 2007;Soba et al 2007). Many of the guidance cues in the semaphorin family and all of those in the ephrin family are transmembrane or surface bound molecules.…”

Section: Tropic Guidance Cuesmentioning

confidence: 99%

Cellular Strategies of Axonal Pathfinding

Raper

Mason

2010

Cold Spring Harbor Perspectives in Biology

157

130

View full text Add to dashboard Cite

Axons follow highly stereotyped and reproducible trajectories to their targets. In this review we address the properties of the first pioneer neurons to grow in the developing nervous system and what has been learned over the past several decades about the extracellular and cell surface substrata on which axons grow. We then discuss the types of guidance cues and their receptors that influence axon extension, what determines where cues are expressed, and how axons respond to the cues they encounter in their environment.T his article provides an overview of how growth cones respond to the cellular substrata and molecular cues they encounter as they extend through the developing nervous system. It elaborates on the primer by Kolodkin and TessierLavigne (2010) and touches on many of the topics covered in greater detail in the articles that follow. The first sections describe how axons extend in a directed manner, the substrata on which they grow, interactions between pioneer and follower axons, and growth cone behaviors in emerging tracts and at decision points. The subsequent sections discuss examples of specific cues, their distributions, how their distributions are determined, and how growth cones integrate multiple cues during pathfinding. AXONS EXTEND IN VIVO IN A DIRECTED MANNERThe first person to visualize the growing tips of axons, Ramon y Cajal, recognized that axons for the most part grow very efficiently towards their ultimate targets. He was a strong advocate for axons finding their way in response to chemotactic cues:"If one admits that neuroblasts are endowed with chemotactic properties, then one might also imagine that they are capable of ameboid movements, initiated by factors secreted from epithelial, neural, or mesodermal elements. As a result, their processes may be oriented in the direction of chemical gradients, and thus guided to the secreting cells" (Ramon y Cajal 1892; trans. English, 1995).This surprisingly modern outlook emphasizing directed guidance was temporarily derailed by the views of Weiss during the 1920s and 1930s. He first argued that functional specificity did not arise as a consequence of specific axonal connections (Weiss 1936), and later argued that nonspecific mechanical guidance cues play a predominant role in guiding axons and organizing them into nerves and tracts

show abstract

“…7). DSCAM may function similarly in other regions of the mammalian nervous system, and this role may extend to other members of the mammalian Dscam gene family.We have identified a spontaneous mutation in mice that creates a loss-of-function allele of Dscam, the Drosophila homologues of which function in both isoneuronal self-avoidance for dendrite arborization and heteroneuronal self-avoidance for axon tiling [7][8][9][10][11][12] . The recessive mutation arose in the BALB/cByJ genetic background and caused an overt neurological phenotype.…”

mentioning

confidence: 99%

Neurite arborization and mosaic spacing in the mouse retina require DSCAM

Fuerst

Koizumi

Burgess

2008

Nature

279

345

View full text Add to dashboard Cite

To establish functional circuitry, retinal neurons occupy spatial domains by arborizing their processes, which requires the selfavoidance of neurites from an individual cell, and by spacing their cell bodies, which requires positioning the soma and establishing a zone within which other cells of the same type are excluded 1 . The mosaic patterns of distinct cell types form independently and overlap. The cues that direct these processes in the vertebrate retina are not known 2,3 . Here we show that some types of retinal amacrine cells from mice with a spontaneous mutation in Down syndrome cell adhesion molecule (Dscam), a gene encoding an immunoglobulin-superfamily member adhesion molecule 4,5 , have defects in the arborization of processes and in the spacing of cell bodies. In the mutant retina, cells that would normally express Dscam have hyperfasciculated processes, preventing them from creating an orderly arbor. Also, their cell bodies are randomly distributed or pulled into clumps rather than being regularly spaced mosaics. Our results indicate that mouse DSCAM mediates isoneuronal self-avoidance for arborization and heteroneuronal self-avoidance within specific cell types to prevent fasciculation and to preserve mosaic spacing. These functions are analogous to those of Drosophila DSCAM (ref. 6) and DSCAM2 (ref. 7). DSCAM may function similarly in other regions of the mammalian nervous system, and this role may extend to other members of the mammalian Dscam gene family.We have identified a spontaneous mutation in mice that creates a loss-of-function allele of Dscam, the Drosophila homologues of which function in both isoneuronal self-avoidance for dendrite arborization and heteroneuronal self-avoidance for axon tiling [7][8][9][10][11][12] . The recessive mutation arose in the BALB/cByJ genetic background and caused an overt neurological phenotype. Mutant and wild-type mice are indistinguishable at birth, but are severely uncoordinated by postnatal day 3 (P3); as adults, the mutant mice have spontaneous seizures and kyphosis, but are fertile and long-lived (.24 months; see http://www.jax.org/research/media/wild_type.html for video). Through positional cloning (see Methods), a mutation was identified in Dscam. Sequencing of genomic and complementary DNA from affected mice revealed a 38-bp deletion in exon 17, causing a frame shift resulting in ten unique amino acids followed by a premature stop codon (Supplementary Fig. 1). This mutation truncates the protein in the second fibronectin repeat (Fig. 1a). Dscam messenger RNA levels in the brain were reduced by 70% in affected mice, consistent with nonsense-mediated decay (Fig. 1b).

show abstract

Drosophila Sensory Neurons Require Dscam for Dendritic Self-Avoidance and Proper Dendritic Field Organization

Cited by 262 publications

References 35 publications

The Conserved Ig Superfamily Member Turtle Mediates Axonal Tiling in Drosophila

The Conserved Ig Superfamily Member Turtle Mediates Axonal Tiling in Drosophila

Cellular Strategies of Axonal Pathfinding

Neurite arborization and mosaic spacing in the mouse retina require DSCAM

Contact Info

Product

Resources

About