Synapse Formation
Establishment of the correct neural circuitry requires growing axons to recognize the appropriate cells as synaptic partners. The photoreceptors that mediate color vision provide us with a simple system in which to examine this process, as photoreceptors that respond to different wavelengths of light project to different target layers in the brain. We have found that the receptor tyrosine phosphatase LAR and its interacting proteins, the Liprins, are required for ultraviolet-sensitive photoreceptors to form synapses with the correct partners, and that LAR signals by a novel mechanism in this process (Hofmeyer et al., PNAS 2006; Hofmeyer et al., PNAS 2009; Astigarraga et al., J. Neurosci. 2010). Using a genetic screen, we have identified Plexin A as an important signal produced by cells in the brain that controls the targeting of photoreceptor axons (Douthit et al., in preparation). We are investigating the possibility that it acts as a ligand for a novel receptor to mediate this effect.
The R1-R6 photoreceptors that mediate motion vision go through a very precise sorting process to connect each axon to the correct target cell. We have found that the immunoglobulin family protein Sidekick plays an essential adhesive role to allow these axons to find their targets (Astigarraga et al., submitted). In epithelia, Sidekick is localized to contacts between three or more cells, and is necessary for normal cell rearrangements. We are searching for proteins that interact with Sidekick to help us understand the mechanism of this effect.

The growth of individual synapses is easier to investigate in the peripheral nervous system. We are using the neuromuscular junction as a model to understand how synapse growth is coordinated with growth of the target muscles during development. We have evidence for local signals downstream of the Insulin receptor pathway that transmit information about muscle size to motor neurons (Ho et al., in preparation).