Identifying regulators of directed neuroblast migration in Caenorhabditis elegans
Guided neuronal migration is an essential process during nervous system development. The Q cell neuroblasts in Caenorhabditis elegans provide a simple and experimentally tractable model system for studies of directed neuronal migration. The Q neuroblasts are born in the same region of the animal and have similar differentiation patterns, yet undergo left-right asymmetric migration, with QR on the right migrating anteriorly and QL on the left migrating posteriorly. QL descendants encounter a posterior EGL-20/Wnt signal, which activates a canonical Wnt signaling pathway to induce expression of the Hox gene mab-5 in QL and QL descendants, but not in QR and QR descendants. MAB-5 is both necessary and sufficient for posterior Q cell descendant migration, as QL descendants migrate anteriorly in mab-5 loss-of-function (LOF) mutants, and QR descendants migrate posteriorly in mab-5 gain-of-function (GOF) mutants. However, it is unknown what genes are regulated by MAB-5 in the Q cells to drive posterior migration. We isolated Q cells from wild-type and mab-5 LOF animals via fluorescence-activated cell sorting and completed RNA-seq to generate novel Q cell transcriptomes. We identified 222 genes that were differentially expressed in the mab-5 LOF Q cells versus wild-type Q cells. We predict that MAB-5 might affect Q cell migration by regulating other transcription factors, RNA processing factors, the cytoskeleton, and cell signaling factors. Thus, we have prioritized candidate transcription factors for functional studies, and identified 13 putative transcription factors that show decreased expression in the mab-5 LOF Q cells versus wild-type Q cells. We predict that these 13 transcription factors require MAB-5 for their expression, and thus may regulate posterior Q cell migration. Indeed, our preliminary functional studies have revealed that several of these putative transcription factors regulate Q cell migration. We anticipate that further functional studies of these candidate mab-5 targets will reveal new insights into directed Q neuroblast migration.