SYNCAM2A IS NECESSARY TO DRIVE SYNAPTOGENESIS IN DEVELOPING DANIO RERIO

Abstract

Synaptogenesis is a vital process for the development of higher cognitive functions such as learning and memory. When the constructive pathways that lead to synapse formation are interrupted, severe neurological disorders such as autism, schizophrenia, and mental retardation can ensue. It is for this reason that the development of synapses merits further investigation. The aim of this project was to characterize a zebrafish synaptic cell adhesion molecule, SynCAM2a, whose human ortholog has been shown to be important for promoting synapse formation in cultured neurons. To determine the protein's function in vivo, SynCAM2a was knocked down with a translation-blocking morpholino and characterized through immunofluorescence and touch response assays. Immunofluorescence showed that SynCAM2a is important for recruiting several pre- and postsynaptic components to the Rohon Beard sensory neuron:Commissural Primary Ascending interneuron synapse, a key constituent of the touch response neuronal circuit. SynCAM2a knock down also showed a 50% reduction in the responsiveness of zebrafish embryos to touch, confirming the necessity of SynCAM2a in constructing this behavioral pathway. Additionally, we found that the intracellular 4.1- and PDZ-binding motifs of SynCAM2a are necessary for promoting synaptic assembly, signifying that both domains are involved in coordinating the recruitment and stabilization of proteins at the pre- and postsynaptic terminals. Together, these findings suggest that SynCAM2a is important for forming the synaptic contacts necessary to develop a functional neuronal network and drive a defined behavior.