Dscam-mediated repulsion controls tiling and self-avoidance

Millard, S. Sean; Zipursky, S. Lawrence

doi:10.1016/j.conb.2008.05.005

Cited by 57 publications

(56 citation statements)

References 23 publications

(33 reference statements)

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“…Most are thought to be inhibitory, and therefore self-limiting, maintaining the precision with which a neuron fires action potentials (46). Normally, neurites are rigorously excluded from contacting their own neuron; in Drosophila, the cell adhesion molecule Dscam1 promotes the repulsion of processes of the same neuron among axons (43) and synapses (25). We tentatively interpret autapses on cell types Mi1 and Dm9 to reflect the reduced effectiveness at these two specific neurons of DScam1-mediated self-exclusion, which normally prevents the self-contact that occurs at autapses.…”

Section: Discussionmentioning

confidence: 99%

“…Combining these lines of evidence (the presence of errors on every cell type, their lack of obvious function, comparability with other error sources, and fewer errors on cells with more synapses) leads us to conclude that ICs simply indicate the accuracy attained by the mechanisms of neuronal synaptogenesis when wiring the medulla. These mechanisms may include the mechanisms of chemoaffinity (42) or those mechanisms involved in exclusion of incorrect connections through selfavoidance (43,44). These mechanisms, along with other cell surface and secreted molecules, are thought to regulate synaptogenesis between synaptic partners, forming the basis for the accuracy of synaptic connections we report.…”

Section: Discussionmentioning

confidence: 99%

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Synaptic circuits and their variations within different columns in the visual system of Drosophila

Takemura

Lǚ

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

379

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We reconstructed the synaptic circuits of seven columns in the second neuropil or medulla behind the fly's compound eye. These neurons embody some of the most stereotyped circuits in one of the most miniaturized of animal brains. The reconstructions allow us, for the first time to our knowledge, to study variations between circuits in the medulla's neighboring columns. This variation in the number of synapses and the types of their synaptic partners has previously been little addressed because methods that visualize multiple circuits have not resolved detailed connections, and existing connectomic studies, which can see such connections, have not so far examined multiple reconstructions of the same circuit. Here, we address the omission by comparing the circuits common to all seven columns to assess variation in their connection strengths and the resultant rates of several different and distinct types of connection error. Error rates reveal that, overall, <1% of contacts are not part of a consensus circuit, and we classify those contacts that supplement (E+) or are missing from it (E−). Autapses, in which the same cell is both presynaptic and postsynaptic at the same synapse, are occasionally seen; two cells in particular, Dm9 and Mi1, form ≥20-fold more autapses than do other neurons. These results delimit the accuracy of developmental events that establish and normally maintain synaptic circuits with such precision, and thereby address the operation of such circuits. They also establish a precedent for error rates that will be required in the new science of connectomics.neural circuits | stereotypy | biological error rates | reconstruction error rates

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Synaptic circuits and their variations within different columns in the visual system of Drosophila

Takemura

Lǚ

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

379

View full text Add to dashboard Cite

show abstract

“…Drosophila DSCAM1, a gene alternatively spliced to produce Ͼ38,000 possible protein isoforms (Schmucker et al, 2000), providing the basis for self-avoidance and tiling (Millard and Zipursky, 2008). 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.…”

Section: Discussionmentioning

confidence: 99%

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

Alves-Sampaio¹,

Troca-Marín²,

Montesinos³

2010

J. Neurosci.

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Down's syndrome cell adhesion molecule (DSCAM) belongs to the Down's syndrome critical region of human chromosome 21, and it encodes a cell adhesion molecule involved in dendrite morphology and neuronal wiring. Although the function of DSCAM in the adult brain is unknown, its expression pattern suggests a role in synaptic plasticity. Local mRNA translation is a key process in axonal growth, dendritogenesis, and synaptogenesis during development, and in synaptic plasticity in adulthood. Here, we report the dendritic localization of DSCAM mRNA in the adult mouse hippocampus, where it associates with CPEB1 [cytoplasmic polyadenylation element (CPE) binding protein 1], an important regulator of mRNA transport and local translation. We identified five DSCAM isoforms produced by alternative polyadenylation bearing different combinations of regulatory CPE motifs. Overexpression of DSCAM in hippocampal neurons inhibited dendritic branching. Interestingly, dendritic levels of DSCAM mRNA and protein were increased in hippocampal neurons from Ts1Cje mice, a model of Down's syndrome. Most importantly, DSCAM dendritic translation was rapidly induced by NMDA in wild-type, but not in Ts1Cje neurons. We propose that impairment of the NMDA-mediated regulation of DSCAM translation may contribute to the alterations in dendritic morphology and/or synaptic plasticity in Down's syndrome.

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“…In numerous cell types, dendritic branches that originate from the same neuron (sister branches) will not cross or fasciculate, and this self-avoidance (see Glossary, Box 2) ensures that dendritic arbors spread evenly across their territory (Grueber et al, 2002; Kramer and Kuwada, 1983;Millard and Zipursky, 2008;Sugimura et al, 2003). By contrast, branches from different neurons can co-exist.…”

Section: Dscam Control Of Dendritic Self-avoidance In Drosophilamentioning

confidence: 99%

Molecules and mechanisms of dendrite development inDrosophila

2009

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Neurons are one of the most morphologically diverse cell types, in large part owing to their intricate dendrite branching patterns. Dendrites are structures that are specialized to receive and process inputs in neurons, thus their specific morphologies reflect neural connectivity and influence information flow through circuits. Recent studies in Drosophila on the molecular basis of dendrite diversity, dendritic guidance, the cell biology of dendritic branch patterning and territory formation have identified numerous intrinsic and extrinsic cues that shape diverse features of dendrites. As we discuss in this review, many of the mechanisms that are being elucidated show conservation in diverse systems. IntroductionDendrites -processes of neurons that are primarily specialized for information input -are one of nature's remarkable architectural feats, and the diverse growth patterns shown by dendritic arbors raise important developmental questions. The particular shapes of dendrites are important in neuronal function and circuit assembly. Their targets and complexity influence the range of inputs that a neuron receives. In addition, the morphology of a dendritic arbor can impact the processing and integration of electrical signals (London and Häusser, 2005). Studies of dendrite morphogenesis therefore seek to understand the developmental origin of arbor shape and to shed light on the significance of particular morphologies for nervous system connectivity and function.Dendrite morphogenesis consists of a series of interrelated steps, which include outgrowth and branching, guidance and targeting, cessation of growth and, in some cases, arbor remodeling (see Box 1). Each process is under extensive genetic regulation and has been the subject of intensive study in recent years. In this review, we highlight recent advances in understanding the molecules and mechanisms that function during these key stages of dendrite morphogenesis. We focus primarily on studies carried out in Drosophila (Fig. 1) and refer to known or emerging areas of conservation in vertebrate systems where appropriate. We focus on several key questions, including: what are the cell biological mechanisms that specify the distribution of dendritic branches along an arbor? How do dendrites achieve typespecific branching patterns? How is specific dendritic targeting controlled in different neurons? How are dendrites instructed when to stop branching and growing? How does activity impact dendrite development in Drosophila? We refer readers to other reviews that cover topics that have thus far been studied primarily in vertebrate systems, including dendritic spine morphogenesis and activitydependent dendrite growth (Alvarez and Sabatini, 2007;Chen and Ghosh, 2005;Flavell and Greenberg, 2008;Lippman and Dunaevsky, 2005;Redmond, 2008). Genetic insights into the cell biology of dendrite growth and branchingThe growth and specialized functions of dendritic arbors can require large investments of dendritic plasma membrane and proteins during development, and, inde...

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Dscam-mediated repulsion controls tiling and self-avoidance

Cited by 57 publications

References 23 publications

Synaptic circuits and their variations within different columns in the visual system of Drosophila

Synaptic circuits and their variations within different columns in the visual system of Drosophila

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

Molecules and mechanisms of dendrite development inDrosophila

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