UC Berkeley

Cellular polarization is critical for many stages of neuronal development, including the asymmetric division of the neuroblast and the axon-dendrite specification of the mature neuron. In C. elegans, Wnt glycoproteins control the polarization of the ALM mechanosensory neurons, but the molecules that mediate Wnt signaling are unclear. I found that the Ror kinase CAM-1, which has been shown to bind to Wnts, is required for ALM polarity. CAM-1 acts in the ALM to promote its polarity and CAM-1 may also have a non-autonomous function in sequestering Wnts. Furthermore, I implicated actin regulators unc-34 and two known components of the Rac pathway, ced-10/Rac and mig-10/lamellipodin, in ALM polarity. Expression of unc-34 and mig-10 from a neuron-specific promoter unc-86 significantly rescued the ALM polarity defect, indicating these genes can function in the neurons. Lastly, I identified that the MIG-15 kinase, a member of the Ste20 kinase superfamily, and potential components of a MIG-15 signaling pathway that might be novel Wnt effectors in neuronal polarity.

Wnts also regulate the asymmetric cell divisions (ACD) of many non-neuronal cell types and the Q neuroblast lineage (Teuliere & Garriga, unpublished observation). The molecules that mediate Wnt signaling in ACD in the Q lineage are unclear. One possible candidate is PIG-1, which is orthologous to vertebrate MELK and belongs to a family of serine/threonine kinases including PAR-1, SAD-1 and AMPK (Cordes et al., 2006). This group of kinases can be phosphorylated and activated by the polarity-regulating kinase LKB1. LKB1 kinase, along with its binding partners STRAD and MO25, have been shown to be master regulators of polarity in many different contexts, and I find that C. elegans orthologs of LKB1, STRAD and MO25 regulate the asymmetric cell division of the Q.p lineage and are potential regulators of PIG-1 in this process.