The vertebrate CNS is comprised of many distinct classes of neural cells with diverse functions, yet almost all neurons and glia are generated from the same source- the neurogenic epithelium which forms the neural plate. As the nervous system develops, appropriate temporal and spatial expansion of precursor populations must be coordinated with regional cell-type specific differentiation. The Drosophila four-jointed (ff) gene encodes a putative secreted signal that acts locally to translate positional information into regional growth and differentiation. Based on the rationale that such a protein with cell-to-cell signaling activity may play an important role in vertebrate neural development, I isolated two Xenopus fj (Xfj) homologs expressed in the neural plate. The goal of this proposal is to determine whether Xfj regulates neural cell proliferation and differentiation with the long term objective of understanding mechanisms that coordinate cell proliferation and differentiation during neurogenesis. In order to assay Xfj function in vivo, the proposed research will utilize the Xenopus embryo, a model system for the study neural patterning. Little is known about the nature of signals that promote proliferation and differentiation during vertebrate neurogenesis. A comprehensive understanding of the action of factors that normally regulate growth and differentiation is important for understanding abnormal development and malignant growth. The high degree of conservation exhibited by fj genes through evolution from flies to frogs to humans is indicative of the potential significance of the fj family of novel signaling factors.