Spinal Cord Neurogenesis We are interested in the functions of Wnt signaling and Tcf function in spinal cord development and regeneration. Our work has shown that Tcf7l1 inhibits the differentiation of spinal cord neural progenitors during embryogenesis. We have also shown that following transection of the larval spinal cord, Wnt signaling is required for radial glia to generate new neurons. One current project in the lab is determining the mechanism downstream of Wnt signaling that mediates neurogenesis following injury. This function may be critical for stem cell-mediated regeneration. A second project is investigating whether new neurons integrate into functional circuitry, and whether they 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, and in the formation of anxiolytic hypothalamic neurons. We have also 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 anxiety.