Optic tract formation: retinal axons' interaction with their pioneers and peers, and a strategy to analyze variants of guidance receptor messengers RNAs

How neural connections are established spontaneously to generate a functioning nervous system remains an important question in the field of developmental biology. Axons and dendrites extended from various cell types have to form at the right place and right time to make appropriate connections. An enormous number of molecules is present in the developing embryos. Experimental analyses are further complicated by virtue of these molecules' ability to interact and affect the function of other molecules. I first set out to test the role of a cell biological mechanism-axon fasciculation-in guiding axon pathfinding within the zebrafish visual system. I then focused on the role of a transmembrane receptor, Robo2, and its splice variants in axon guidance. In Chapter 1, I present some important questions in axon guidance and alternative splicing, along with reviews of factors involved in retinal axon guidance. I also introduce the roles of alternative splicing in increasing protein diversity and thus contributing to various responses in pathfinding along the axon trajectory. Chapter 2 is a collaborative peer-reviewed paper published in Development showing that early-born retinal ganglion cells guide later-born cells within and outside of the eye. In Chapter 3, I described my observation of robo2 alternative splice forms in developing zebrafish embryos and my experiments using morpholinos to test the domains iv functionally. Finally, Chapter 4 discusses the findings and future directions of the studies.