Examining development and function of pretectal visual neural circuits in gs homeobox 1 mutant zebrafish

Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. This dissertation identifies, for the first time, multiple roles for genomic screen homeobox 1 (gsx1), in the development and function of zebrafish visual neural circuits. First in chapter 2, gsx1 is identified as playing an important role in the differentiation of pretectal neurons expressing vesicular glutamate transporter 2a (vglut2a). Next, vglut2a-expressing pretectal neurons are shown to be required for proper termination of retinal input to the pretectum (Pr). Lastly, gsx1 mutants are observed to have deficits in the visually mediated behavior of prey capture that are linked to the morphological changes in pretectal neural circuit formation. In chapter 3, the neurochemical identity of a subset of pretectal neurons is explored to the presence and absence of functional Gsx1 to deepen our understanding of pretectal cell differentiation. Chapter 4 also provides a review of functional associations tied to individual pretectal visual neural circuits and, an overview of current tools to decipher genetic and molecular mechanisms contributing to their development. New combinations of neurogenetic techniques to assess pretectal development in ways restricted to individual visual neural circuits are presented. In summary, using zebrafish, the research presented in this dissertation reveals novel roles for gsx1 in the differentiation of pretectal neurons that guide visual input to the correct terminal locations, leading to appropriate visual mediated responses. Together, understanding the genetic programs required for neurodevelopment are instrumental in our pursuit of uncovering the biological underpinnings of visual dysfunction related to NDDs