Judith S. Eisen
Research in my lab is focused on understanding how embryonic cells acquire and express their fates, using the zebrafish as a model. Our studies have concentrated on a small set of identified neurons that innervate axial muscles, neural crest cells, and more recently two derivatives of the somites, muscle and sclerotome. In each case, we have begun our studies with a cellular approach, learning about the lineages that produce the cells of interest and the details of their differentiation. We then challenge the cells by altering their environment, to learn when their fates become specified and how this process is affected by the embryonic milieu. Finally, we use genetic and molecular approaches to learn about the mechanisms underlying the cellular processes revealed by our experiments.
We know most about the processes underlying development of identified motoneurons. The muscle derived from each somite is innervated by 3-4 motoneurons that can be individually identified by their cell body positions within the spinal cord, the regions of the muscle in which they arborize, and the times at which they extend axons. We have found that initially all of these cells have the potential to develop as any one of the motoneurons but later they become committed to develop into specific motoneurons. This process appears to depend on their cell body positions within the spinal cord, suggesting that they are responding to positionally-distinct signals. Interestingly, two of these cells remain equivalent, even after the others have become committed to distinct fates. Theses two cells appear to compete to survive and become a functional motoneuron.
We have begun to uncover molecular mechanisms involved in specifying the fates of the identified motoneurons. Our first approach has been to test the roles of candidate genes cloned by homology with genes from other species. For example, we have used single cell transplantation experiments to show that expression of the LIM domain homeobox gene islet2 is correlated with the fate of only one type of motoneuron. We have also used differential display PCR to isolate zebrafish genes expressed specifically in the motoneurons at appropriate developmental stages. Finally, we have generated and begun to analyze mutants that affect development of specific motoneurons.
Our most recent studies focus on induction of motoneurons. Work from other vertebrates has implicated axial structures in motoneuron induction. By studying mutants lacking axial structures, we have learned the induction of the identified motoneurons can be separated from induction of later-developing motoneurons. We are now beginning to examine the molecular mechanisms involved in competence of prospective motoneurons to respond to inductive signals.