Transcriptional Regulation of Axon Pathfinding

different species and neuron types. Some are candi-† Neuron dates for being direct regulators of the molecules that Cell Press confer pathfinding specificity. In each system dis-Cambridge, Massachusetts 02138 cussed, the projection phenotypes of the neurons involved had been described previously so that alterations in pathfinding were easily recognized. Neuronal differentiation has been postulated to occur Pathfinding versus Cell Fate Determination: in a series of stages. These stages have been defined Transcription Factors Expressed differently in various species. In vertebrates, one of the in Neuron Precursors earliest decisions identified to date is whether to be-Many genes that encode transcription factors, when come a neuron or glial cell. Later stages of differentiation mutated, will give rise to defects in axonal projection define the details of the individual neuronal phenotype. patterns. But this phenotype alone is not sufficient to In invertebrates, such as Drosophila, where individual classify a gene as a direct regulator of expression of cells can be more readily identified and followed through molecules controlling pathfinding. The genes described various stages, the decision points have been defined in this section are expressed early in neural cell lineages. in more detail, from the early delamination of identified Since axon outgrowth occurs in postmitotic neurons, neuroblasts from the epithelium, the assignment of phe-pathfinding defects resulting from mutation of these notypic classes to the progeny of these neuroblasts, to genes are most likely an indirect manifestation of the the final choice of individual neuronal fates. In all ner-disruption of cell fate determination and differentiation. vous systems, the ultimate outcome of cell fate specifi-The gene prospero (pros) has been identified in sev-cation for a neuron is the completion of synapse forma-eral searches for genes that control cell fate in Drosoph-tion with its appropriate target cell(s). Indeed, the mature ila (Doe et al., 1991; Vaessin et al., 1991). pros is ex-identity of a neuron is defined by its pathway and target pressed in most or all neuroblasts of the CNS and PNS. choices. In pros mutants, neuroblasts gave rise to the normal Axon pathfinding is one aspect of the differentiation number and types of neurons, but there are severe de-program of a neuron that occurs after the final cell divi-fects in the formation of major axon tracts. pros appears sion. As an axon grows away from the neuronal cell to act early in the differentiation pathway at the step body, it must choose among the …