The role of heparan sulfates in the development and function of the nervous system

Abstract

The nervous system regulates complex behaviors through a network of neurons interconnected by synapses. However, how these are genetically predetermined is still unclear. Male mating is the most complex behavior in C. elegans . It is composed of sequential steps that are governed by more than 3,000 chemical connections. In this work, I show that heparan sulfate (HS) play a role in the formation and function of the male neural network. HS modification enzymes and HS proteoglycans (HSPG) were required for the anteroposterior and dorsoventral axonal migration of male-specific sensory neurons. Specifically, dorsoventral axonal migration of RnB was achieved through regulation of netrin signaling. Furthermore, cell-autonomous and non- autonomous 3-O sulfation by the HS modification enzyme HST-3.1, localized to the HSPG glypicans LON-2 and GPN-1, was specifically required for response to hermaphrodite contact during mating. Loss of 3-O sulfation in the postsynaptic cell, resulted in accumulation of mCherry