Genetic control of left/right asymmetry in C. elegans neuroblast migration

Abstract

The migration of cells is crucial for proper animal development. In order to study cell migration in an in vivo context we used the small nematode C. elegans as a model organism. During C. elegans larval development two Q neuroblasts, initially positioned on equivalent left/right positions, migrate in opposite directions along the anteroposterior axis. Previous studies showed that the Wnt target gene mab-5 is expressed in a left/right asymmetric manner and that it is essential for the left/right asymmetric migratory behavior. In this thesis we studied a variety of aspects of the left/right asymmetric migration of Q neuroblasts. First, we showed that a combination of positive and negative transcriptional feedback interactions within the Wnt pathway results in activation of mab-5 expression to a stable range exhibiting low expression variability. Furthermore, the initial polarization of Q neuroblasts that precedes Wnt signaling activation was found to be necessary for the proper left/right asymmetric mab-5 expression. While analyzing mutants in which the initial polarization was affected we found that posterior initial polarization positively correlates with the upregulation of mab-5 expression. Finally, we showed that several genes encoding transmembrane proteins act together in partially overlapping genetic pathways to ensure proper initial Q neuroblast polarization. The studies described in this thesis have provided a basic genetic framework that controls the initial Q neuroblast polarization and unraveled how proper initial polarization results in the robust left/right asymmetric expression of the Wnt target gene mab-5.