Cell-cell interactions in dendrite development

How are dendritic territories established?  How do cell-cell interactions determine where and how dendrites receive sensory or synaptic input?   What are the cellular and molecular mechanisms of tiling and self-avoidance?

Dendritic arbors fill characteristic territories, and these territories determine where and how they receive sensory or synaptic input.  We have been interested in two patterns of organization common to dendrites and axons, termed tiling and self-avoidance.  Tiling refers to the complete but non-overlapping coverage of receptive areas, typically by cells of the same function.  Self-avoidance refers to the tendency of dendrites from the same neuron to avoid fasciculation.  We are interested in the cellular and molecular mechanisms of dendrite-dendrite interactions that promote tiling and self-avoidance.  Our investigations of self-avoidance have led to the discovery of important roles for the cell surface receptors Dscam1 and integrins.

Dscam1 is a cell surface protein of the immunoglobulin superfamily that comes in a number of different isoforms, or variants that differ in particular parts of protein.  Work from Larry Zipursky's lab (UCLA) found that alternative splicing of Dscam1 can generate over 38,000 distinct protein forms, with a little over 19,000 of these differing in their extracellular recognition domain.  Our data suggested a model in which Dscam1 diversity is important for generating many individual surface identities of neurons.  Surface identity underlies the neuron's ability to identify sister branches as coming from the same cell, from which they are repelled, and to discriminate branches coming from different cells, with which they co-exist. 

Our studies of integrin receptors identified another parallel pathway that supports self-avoidance in sensory neurons.  Body wall sensory dendrites arborize mostly in a planar, two-dimensional arrangement.  Integrins allow dendrites to adhere to the nearby extracellular matrix and maintain their 2D arrangement.  2D restriction allows dendrites to come into contact and recognize other dendrites through the Dscam1-dependent mechanism.