Integrins Regulate Repulsion-Mediated Dendritic Patterning of Drosophila Sensory Neurons by Restricting Dendrites in a 2D Space

Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Neuron (Impact Factor: 15.05). 01/2012; 73(1):64-78. DOI: 10.1016/j.neuron.2011.10.036
Source: PubMed


Dendrites of the same neuron usually avoid each other. Some neurons also repel similar neurons through dendrite-dendrite interaction to tile the receptive field. Nonoverlapping coverage based on such contact-dependent repulsion requires dendrites to compete for limited space. Here we show that Drosophila class IV dendritic arborization (da) neurons, which tile the larval body wall, grow their dendrites mainly in a 2D space on the extracellular matrix (ECM) secreted by the epidermis. Removing neuronal integrins or blocking epidermal laminin production causes dendrites to grow into the epidermis, suggesting that integrin-laminin interaction attaches dendrites to the ECM. We further show that some of the previously identified tiling mutants fail to confine dendrites in a 2D plane. Expansion of these mutant dendrites in three dimensions results in overlap of dendritic fields. Moreover, overexpression of integrins in these mutant neurons effectively reduces dendritic crossing and restores tiling, revealing an additional mechanism for tiling.

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    • "The expression of the β-neu-subunit is restricted to the mid gut, and its function is not known. Recent observations have also stressed the role of the fruit fly integrin–laminin interaction in the attachment of the dendrites to the ECM and in the control of dendrite positioning (Han et al. 2012; Kim et al. 2012). The nematode Caenorhabditis elegans has two integrin α-subunits (ina-1 and pat-2) and one β (pat-3) generating two heterodimeric integrins. "
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    ABSTRACT: The extracellular matrix and cell adhesion receptors, especially the integrins, have played a major role in the emergence of multicellular animals. The members of the integrin family can be found in all present-day metazoans, and they actually predate the origin of the animal kingdom. Chordate integrins show structural and functional diversity, and they gather around themselves a large number of adaptor and signaling proteins, an adhesome. This chapter reviews the early evolution of integrin-type protein domains, the origin of integrin-dependent adhesion mechanisms, and the later developments in chordate-specific integrins.
    Evolution of Extracellular Matrix, 01/2013: pages 243-283;
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    • "Golgi outposts are small enough to be trafficked into terminal branches that are 150–300 nm in diameter (Han et al., 2012; Ye et al., 2007), and therefore may provide an excellent vehicle for transporting nucleation machinery to these remote areas of the arbor. It will be interesting to determine how these nucleation factors are recruited to the Golgi outposts. "
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    ABSTRACT: Microtubule nucleation is essential for proper establishment and maintenance of axons and dendrites. Centrosomes, the primary site of nucleation in most cells, lose their function as microtubule organizing centers during neuronal development. How neurons generate acentrosomal microtubules remains unclear. Drosophila dendritic arborization (da) neurons lack centrosomes and therefore provide a model system to study acentrosomal microtubule nucleation. Here, we investigate the origin of microtubules within the elaborate dendritic arbor of class IV da neurons. Using a combination of in vivo and in vitro techniques, we find that Golgi outposts can directly nucleate microtubules throughout the arbor. This acentrosomal nucleation requires gamma-tubulin and CP309, the Drosophila homolog of AKAP450, and contributes to the complex microtubule organization within the arbor and dendrite branch growth and stability. Together, these results identify a direct mechanism for acentrosomal microtubule nucleation within neurons and reveal a function for Golgi outposts in this process.
    Neuron 12/2012; 76(5):921-930. DOI:10.1016/j.neuron.2012.10.008 · 15.05 Impact Factor
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    • "It has been shown that the extracellular matrix (ECM) secreted by the epidermis makes significant contributions to shaping dendritic arbors of da neurons. In larvae, dendrite–substrate interactions ensure preventing crossings of isoneuronal branched or self-avoidance (Han et al. 2012; Kim et al. 2012), whereas local degradation of the ECM in newly eclosed adults plays a pivotal role in reshaping radial arbors of v'ada into the lattice shape (Yasunaga et al. 2010). It could be that branch elongation of v'ada and ldaA/A-like neurons may be particularly promoted in a spatially restricted fashion by an unknown ECM distribution between the cell bodies of the two cell types, which secondarily results in the dendrite–dendrite contact. "
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    ABSTRACT: Neuronal circuits that are formed in early development are reorganized at later developmental stages to support a wide range of adult behaviors. At Drosophila pupal stages, one example of this reorganization is dendritic remodeling of multidendritic neurons, which is accomplished by pruning and subsequent regeneration of branches in environments quite distinct from those in larval life. Here, we used long-term in vivo time-lapse recordings at high spatiotemporal resolution and analyzed the dynamics of two adjacent cell types that remodel dendritic arbors, which eventually innervate the lateral plate of the adult abdomen. These neurons initially exhibited dynamic extension, withdrawal and local degeneration of filopodia that sprouted from all along the length of regenerating branches. At a midpupal stage, branches extending from the two cell types started fasciculating with each other, which prompted us to test the hypothesis that this heterotypic contact may serve as a guiding scaffold for shaping dendritic arbors. Unexpectedly, our cell ablation study gave only marginal effects on the branch length and the arbor shape. This result suggests that the arbor morphology of the adult neurons in this study can be specified mostly in the absence of the dendrite-dendrite contact.
    Genes to Cells 11/2012; 17(12). DOI:10.1111/gtc.12008 · 2.81 Impact Factor
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