EGFR signaling regulates synaptic connectivity via Gurken

The synapse is the essential unit of neural function. It is critical to understand how synapses form during development, how they are maintained throughout the life of an organism, and how their structure and function are affected by neural activity. An understanding of these aspects of synapses will likely provide insight into the etiology of neurodevelopmental disorders such as autism, mental retardation or epilepsy. To identify novel regulators of synaptic development, I screened for mutants with defects in synaptic morphology and growth at the Drosophila larval neuromuscular junction: NMJ). My screen identified several mutants with defects in various aspects of synaptic development. I pursued a more in depth analysis of an identified mutant, happyhour, with defects in synaptic target selection. Synaptic target selection is critical for establishing functional neuronal circuits. The mechanisms regulating target selection remain incompletely understood. I describe a role for the EGF receptor and its ligand Gurken in target selection of octopaminergic Type II neurons in the Drosophila neuromuscular system. Mutants in happyhour, a regulator of EGFR signaling, form ectopic Type II neuromuscular junctions. These ectopic innervations are due to inappropriate target selection. I demonstrate that EGFR signaling is necessary and sufficient to inhibit synaptic target selection by these octopaminergic Type II neurons, and that the EGFR ligand Gurken is the post-synaptic, muscle-derived repulsive cue. These results identify a new pathway mediating cell-type and branch-specific synaptic repulsion, a novel role for EGFR signaling in synaptic target selection, and an unexpected role for Gurken as a muscle-secreted repulsive ligand.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biology and Biomedical Sciences: Developmental, Regenerative and Stem Cell Biology

Year dc:date.available

2011

Author dc:creator

• Naylor, Sarah

Contributors dc:contributor

• Aaron DiAntonio

• Developmental biology
• Neurosciences
• drosophila
• EGFR
• Gurken
• synaptic targeting

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K7WM1BDD

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1624