2004 East Coast Worm Meeting abstract 61
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Skirball Institute, NYU School of Medicine, New York, New York
Each neuron type in C. elegans projects axons with characteristic trajectories along the dorsoventral and/or anteroposterior body axes. Axons extend from the cell body at distinct orientations, revealing an intrinsic cellular polarity. Although evident in a mature neuron, when or how neuronal polarity is established is unclear. In addition, the processes that direct growth cone extensions along the anteroposterior body axis are poorly understood. To gain insight into the molecular mechanisms that determine neuronal polarity and anteroposterior axon guidance, we have begun screens for mutants with defects in the growth of the AVG axons. AVG is located in the retrovesicular ganglion and projects a very short anteriorly directed process and a long posteriorly directed process that extends to the tail. AVG pioneers the right ventral nerve bundle and is thought to provide cues that promote the proper assembly and organization of the ventral nerve cord.
We isolated several mutations that alter AVG axonal outgrowth. zd101 caused the anteriorly directed AVG axon to over extend and enter the nerve ring; the posteriorly directed axon was unaffected. zd101 is an allele of klp-7, which encodes a kinesin-related protein involved in the regulation of microtubules. We had found previously that klp-7 mutations cause neurons that normally extend only a single axon to project a second axon. Together these observations indicate that the regulation of microtubules can influence both the initiation and termination of axon extension.
Several mutations were recovered that cause the apparent reversal of AVG anteroposterior polarity, as defined by the lengths of anterior and posterior axons. These mutants exhibited a range of three AVG axonal phenotypes: animals with a wildtype anterior axon and a posterior axon shorter than wild type, animals with anterior and posterior processes about equal in length and animals with a very long anterior axon and a very short or no posterior axon. When the axons were about equal in length, the anterior process terminated in the nerve ring and the posterior process stopped before the vulva. However, when the posterior axon was absent and the anterior axon was very long, the long axon typically entered the nerve ring and the looped back to the tail via the dorsal cord or lateral fascicle. These observations suggest that if the neuronal polarity of AVG is completely reversed, the long axon can be guided to the tail and that the AVG guidance cues are not restricted to the ventral nerve cord. Furthermore, these cues might only influence the direction of growth and not extension per se. We also found several genes that influence the anteroposterior polarity of other neurons, suggesting that multiple processes are involved in the establishment of anteroposterior neuronal polarity.