Spinal Cord Neurogenesis We are interested in the functions of Wnt signaling in spinal cord development and regeneration. Our work has shown that repression of Wnt targets maintains a quiescent pool of radial gilal progenitors in the embryonic spinal cord. Following spinal cord injury, Wnt signaling is required for radial glia to generate new neurons that integrate into functional locomotor circuitry. A current project in the lab is determining the molecular mechanisms downstream of Wnt signaling that mediate neurogenesis following injury. Identifying Wnt target genes required for regeneration in zebrafish could lead to candidates for therapeutic approaches in human spinal cord injury. A second project is investigating whether new neurons that integrate into functional circuitry are required for the recovery of sensory and motor behavior. Hypothalamic Neurogenesis This work focuses on the role of Wnt and Lef1 activity in the differentiation of neural progenitors in the posterior hypothalamus. This region of the brain maintains Wnt activity and continues to produce neurons throughout life, suggesting that Wnt-regulated neurogenesis plays an important role in the adult brain. We have found an evolutionarily conserved requirement for Lef1 in mediating anxiety-related exploratory behavior, through the differentiation of hypothalamic neurons. We have identified Lef1 target genes in the zebrafish and mouse hypothalamus, and are determining their functions in neurogenesis and behavior. Current work is also focused on testing the requirement for postembryonic neurogenesis in modulating innate behavior.