Regulation of neuronal polarity in C. elegans by TOE-2 and Wnt signaling

Cellular polarization is an important aspect of neural development. During the development of the C. elegans nervous system, many divisions are asymmetric and give rise to neurons and cells that die. While we understand how cells die in C. elegans, we know much less about how cells are instructed to adopt the apoptotic fate. To address this issue, I studied the Q.p neuroblast, which divides to produce a larger anterior cell and a smaller posterior cell that dies. The surviving Q.p daughter divides again to form the neurons A/PVM and SDQ. A forward-genetic screen for mutants with extra A/PVMs in order to identify genes that regulate the apoptotic fate was conducted previously in the lab. A mutant, gm389, was isolated. In gm389, I identified a mutation in the gene toe-2, which encodes a target of the worm ERK ortholog, MPK-1. I found that TOE-2 not only regulates the apoptotic fate of the posterior Q.p daughter, but it also plays a role in the asymmetric division of Q, the mother of Q.p. I found that TOE-2 functions autonomously in the Q lineage where it regulates several asymmetric cell divisions (ACDs). I also show that, during Q lineage cell divisions, TOE-2 localizes to centrosomes, to the posterior cortex and at the site where the cleavage furrow will form.Cellular polarization is also required for the function of mature neurons. The function of a neuron is facilitated by its distinct morphology. Electrical signals are propagated along neuronal processes that extend from the cell body to form connections with muscle cells, sensory structures or other neurons. In vitro studies of developing neurons have shown that a neuronal process forms at random from one of many smaller processes protruding from the developing cell. Many intracellular molecules necessary for this process have been identified. However, many neurons display invariant polarity in vivo, suggesting specific regulation of the polarization process by external signals. Wnts and Frizzled receptors have been shown to direct polarization of mechanosensory neurons along the C. elegans anterior/posterior (AP) axis. It was shown that ectopic expression of MIG-1 in PLM reverses PLM polarity. I show that ectopic expression of the cysteine-rich domain of MIG-1 in PLM is not sufficient to cause a polarity reversal. I also show that the activity of MIG-1 in PLM is dependent upon the Wnt EGL-20