The formation of appropriate connections between motoneurons and their target muscles is essential for animals to carry out their normal behavioral repertoire. Motoneuronal axons navigate through the developing embryo towards target muscles in a highly stereotyped manner making few navigational errors. The precision of this event is astonishing considering the complicated environment of a developing embryo and the distances many axons travel. Research over the past two decades has demonstrated that axon pathfinding is directed by interactions between the tip of the growing axon and guidance cues, either positive or negative, present in the environment. Although our knowledge of the cellular and molecular aspects of axonal guidance has increased, numerous questions remain unanswered. In particular, it is unclear how axons interact with different pathway environments and how axon pathways are established during development. Using zebrafish as a model system, Dr. Beattie will address how a set of identified motoneuronal axons locate their correct target muscles. The zebrafish neuromuscular system offers a unique opportunity for studying this issue. Individually identifiable primary motoneurons pathfind along and innervate distinct muscle regions, thus enabling analysis of single motoneurons. Using a combination of mutational analysis, cell transplantation and molecular analysis, the experiments outlined in this proposal will reveal how axons interact with cells along their pathway, how motoneuronal pathways are established during development and how myotomes develop regions displaying unique properties with respect to growing axons. This investigation will impact the field by uncovering the events that control this essential component of axon guidance.
