Dr. Pierchala's laboratory investigates how neurotrophic factors guide the development and maintenance of the nervous system. They focus predominantly on a family of neurotrophic factors known as the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs). The GFLs are comprised of four homologous molecules (GDNF, neurturin, artemin, and persephin) that are critical for neural development, kidney morphogenesis, and spermatogenesis.  GFLs, such as neurturin, are also required for the maintenance of the metabolic and phenotypic status, i.e. “trophic” status, of adult neurons.  The neurotrophic activities of GFLs are conveyed via activation of their receptor tyrosine kinase, c-Ret. GFLs do not bind directly to Ret to activate it, but instead bind with high affinity to GPI-anchored coreceptors termed GFRas that, as a GFL-GFRa complex, activate Ret.