Defining the role of tcf15 in Danio rerio peripheral nervous system patterning

The peripheral nervous system (PNS) is an intricately patterned network of axons and glial cells that communicates sensory and motor information throughout the body. During development, axons and glia migrate in close association from their site of origin to their eventual site of innervation. Currently, the suite of molecular cues that govern this patterning process is incompletely understood. In order to further understand the genetic underpinnings of PNS development, we studied the stl159 zebrafish mutant which exhibits defects in posterior lateral line axon-glial patterning. We found that PNS patterning anomalies were not confined to the lateral line system within stl159 mutants and that the motor nerves of stl159 mutants were disorganized compared to wild-type siblings. Furthermore, we found that disrupting expression of the muscle development gene tcf15 using the genome-editing tool CRISPR-Cas9 induced a phenocopy of the stl159 mutation, demonstrating that a single nucleotide polymorphism (SNP) within the tcf15 gene is likely causative for the stl159 mutant phenotype. Given that tcf15 is normally expressed in muscle tissue during development, we predict that tcf15 influences PNS patterning non-cell-autonomously by facilitating the development of muscle tissue that contains cell guidance molecules utilized by migrating axons and glia. Current work uses a muscle tissue-specific expression vector to clarify the non-cell-autonomous roles of tcf15 in PNS development. Overall, our results implicate tcf15 as a novel factor in PNS axon-glial patterning and provide evidence for the importance of muscle-derived signaling cues in PNS development