845A Poster - 13. Neural development and physiology
Thursday April 07, 2:00 PM - 4:00 PM

Author:
Heather Broihier

Affiliation: Case Western Reserve University

Keywords:
m. CNS; j. other signaling pathways

­Developmental neurobiologists have been consumed with elucidating how circuits are built and remodeled since the 1940s when Roger Sperry formulated the chemoaffinity hypothesis. Their work has led to key insights into molecular mechanisms responsible for driving axon guidance, target recognition, and synaptogenesis. What is much less clear is how these generative processes are balanced with degenerative processes. Neurons that are damaged, those with aberrant electrical activity, or lacking trophic support often undergo apoptosis during development and in the adult. And at a smaller scale, pruning of neurites and synapses is key to circuit remodeling and plasticity.
Toll-like receptor (TLR) pathways were first identified for their roles in embryonic patterning in flies and have since been defined as a conserved centerpiece of innate immunity. My lab elucidated functions of TLR signaling in neural development, specifically at the NMJ. We then made the unexpected discovery that one of the most pronounced phenotypes associated with loss of Toll-6 function, a dramatic increase in the number of apoptotic neurons during development, is caused by selective loss of Toll-6 function not in neurons, but rather in glia. We demonstrated that release of the Toll-6 ligand, Spz5, from dying neurons activates a novel Toll-6 pathway in glia to prime them for phagocytosis. I will discuss recent progress my laboratory has made defining the functions of TLR signaling in regulating neuron-glia interactions in synapse, neurite, and neuron elimination across lifespan.