Our lab is interested in understanding how neurotrophic growth factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), regulate nervous system development and function. We study neurotrophin action through the identification of gene products that these growth factors regulate in the CNS and PNS, determining how these proteins are involved in neurogenesis, axonal outgrowth and pathfinding, synaptogenesis, and synaptic plasticity, using cellular and molecular tools, and knockout mouse models. Together with the Benson lab, we're currently examining how the NGF-regulated cell surface adhesion protein, called NILEGP or L1, an immunoglobulin (Ig) superfamily member that is expressed primarily in the nervous system, regulates axonal outgrowth, branching, pathfinding, and fasciculation, as well as neuronal migration. Of note, inherited X-linked mutations in L1 result in hydrocephalus and mental retardation (CRASH and MASA syndromes). In addition, we're trying to understand how the neurotrophin-inducible gene Vgf, encoding a secreted ‘granin-like’ protein and peptide precursor, controls energy expenditure, memory, and depressive behavior. Recent collaborative studies with the Huntley, Alberini, Shapiro, and Duman laboratories indicate that VGF-derived peptides injected into the brain have anti-depressant efficacy, consistent with abnormalities noted in memory tasks and depressed behavior in VGF knockout mice, and that VGF regulates hippocampal synaptic activity via a BDNF-dependent mechanism. We are developing novel conditional and humanized knockout models to better understand VGF function in the developing and adult hippocampus, hypothalamus, and sympathetic nervous system.