Title

Neurite placement and synapse formation in layered neuropils

Date of Award

Spring 2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology

First Advisor

Colón-Ramos, Daniel

Abstract

A fundamental design principle of nervous systems is the grouping of neuronal contacts into layers within nerve bundles. The layered arrangement of neurites requires nanoscale precision in their placement within bundles, and this precision, which cannot be exclusively explained by simple tip-directed outgrowth dynamics, underpins synaptic specificity and circuit architecture. For my thesis work, I implemented novel dynamic imaging methods and analyses and constructed fluorescent labeling tools to document the specific placement of single neurites during the assembly of the C. elegans nerve ring. We uncover a zippering mechanism that controls precise placement of neurites onto specific layer subdomains. Through forward and reverse genetic screens, I identified several molecular pathways that affect zippering-mediated neurite placement. For a major part of my thesis work, I have focused on one of these molecules, the Ig family cell adhesion molecule, SYG-1. Nanoscale precision in neurite placement is orchestrated via temporally-regulated expression of SYG-1 during embryonic development. SYG-1 acts as an instructive signal, defining sublaminar regions and guiding neurite zippering onto target neurons. Our study suggests that adhesion-mediated zippering mechanisms might be important developmental mechanisms that coordinate neurite placement and synaptic specificity within brain neuropil bundles in vivo. Our observations also suggests that differential adhesion might act as an organizational principle in the C. elegans nervous systema, sorting neurites into specific nerve ring layers.

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