Book Description

Abstract: The relative simplicity of the early zebrafish nervous system makes it an attractive model for studying vertebrate nervous system development. Mutagenesis screens in zebrafish have been undertaken to identify new genes involved in different aspects of nervous system development. We have characterized an ENU induced mutation in zebrafish deadly seven/notch 1a (des), which perturbs neurogenesis, somitogenesis, and motor axon outgrowth. The neurogenic defect is manifested as an increase in hindbrain interneurons and spinal motoneurons. In addition, we find a decrease in the number of spinal sensory neurons, and an increase in sensory neurons derived from neural crest cells. This data demonstrates that Notch signaling is important for determining the number of specific neuronal cell types during early nervous system development. The somite defect in des mutants is revealed by abnormalities in somite/myotome boundary formation and somite/myotome gene expression in the mid- and posterior trunk and tail. Each somite/myotome in wild-type embryos contains an anterior and posterior domain. This anterior-posterior somite patterning is disrupted in des mutant embryos. Our studies reveal that this patterning defect causes aberrant motor axon outgrowth. Motor axons in wild-types obey domain restrictions, never entering the posterior domain. However, in des mutant embryos, motor axons are seen in both domains. Thus, proper patterning of the somite is essential for stereotyped motor axon pathfinding. The des mutation results in a dramatic increase in the hindbrain interneuron, Mauthner (Mth). This neuron is an integral part of a relatively simple neural circuit driving the escape response in zebrafish and thus presents an excellent opportunity to study properties of neural circuit formation. Due to the presence of supernumerary Mth cells in des mutants; we analyzed the affect of having one cellular component of this circuit dramatically increased on circuit formation and behavior. Our results indicate that all of the supernumerary Mth cells are integrated into the circuit and the circuit is functional. The escape behavior of des mutants is very similar to wild-type embryos. We found, however, that individual Mth cells in des mutants contacted fewer target cells in the spinal cord than Mth cell in wild-type larvae. These data indicate that when there are more Mth cells present, they divide up the territory thus incorporating all cells into the circuit yet maintaining a normal escape response behavior. This study demonstrates that there is plasticity in the formation of the escape response circuit in zebrafish.