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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    • "Second, the PG formed aggregates instead of the normal monolayer, resulting in a greater OS diameter (Fig. 2F). These OS phenotypes were rescued by co-expressing a βPS transgene with the βPS-RNAi in glia (Fig. 2G), along with the αPS2 subunit to block the dominant-negative effects of βPS alone (Han et al., 2012). "
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    ABSTRACT: Many aspects of glial development are regulated by extracellular signals, including those from the extracellular matrix (ECM). Signals from the ECM are received by cell surface receptors, including the integrin family. Previously, we have shown that Drosophila integrins form adhesion complexes with Integrin-linked kinase and talin in the peripheral nerve glia and have conserved roles in glial sheath formation. However, integrin function in other aspects of glial development is unclear. The Drosophila eye imaginal disc (ED) and optic stalk (OS) complex is an excellent model with which to study glial migration, differentiation and glia-neuron interactions. We studied the roles of the integrin complexes in these glial developmental processes during OS/eye development. The common beta subunit βPS and two alpha subunits, αPS2 and αPS3, are located in puncta at both glia-glia and glia-ECM interfaces. Depletion of βPS integrin and talin by RNAi impaired the migration and distribution of glia within the OS resulting in morphological defects. Reduction of integrin or talin in the glia also disrupted photoreceptor axon outgrowth leading to axon stalling in the OS and ED. The neuronal defects were correlated with a disruption of the carpet glia tube paired with invasion of glia into the core of the OS and the formation of a glial cap. Our results suggest that integrin-mediated extracellular signals are important for multiple aspects of glial development and non-autonomously affect axonal migration during Drosophila eye development.
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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.
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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.
    Preview · Article · Dec 2012 · Neuron
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