Roles for the adhension molecule Contactin2 in the development and function of neural circuits in zebrafish
Neuronal migration and axon guidance are critical developmental processes that are essential for establishing functional neural circuits underlying complex cognitive and motor functions. Precise neuronal migration and axon guidance are dependent upon cell-cell and cell-substrate interactions, which are mediated by several membrane-associated molecules. The relatively concise segmental organization of the hindbrain and the simple scaffold of axon tracts in the zebrafish brain provides an ideal model to study how different molecules collaborate to guide migrating neurons and growing axons to their final location. In this thesis, I examine the roles of membrane molecules during neuron migration and axon guidance in zebrafish. In Chapter 3, I show the generation of Contactin2 (Cntn2) null mutant using CRISPR/Cas9 and characterize cntn2 mutant. I demonstrate a role for cntn2 in facial branchiomotor (FBM) neuron migration and fasciculation of medial longitudinal fascicle (MLF) axons. In addition, using touch-evoked escape response and swimming assays, I show sensorimotor deficits in cntn2 mutants. Collectively, these data demonstrate distinct developmental roles for zebrafish cntn2 in neuronal migration and axon fasciculation, and in the function of sensorimotor circuits. In Chapter 4, I examine pairwise genetic interactions between several PCP and non-PCP genes for FBM neuron migration. I show that vangl2 is rather unique in exhibiting genetic interactions with several PCP and non-PCP genes. These data suggest that vangl2 might be playing a central role in regulating the function of many PCP and non-PCP genes for FBM neuron migration. In Chapter 6, I describe a novel genetic approach which utilizes the human CD59 receptor (hCD59) and the bacterial toxin intermedilysin (ILY) for rapid cell ablation in zebrafish.
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