The Collagens DPY-17 and SQT-3 Direct Anterior-Posterior Migration of the Q Neuroblasts in C. elegans.

Cell adhesion molecules and their extracellular ligands control morphogenetic events such as directed cell migration. The migration of neuroblasts and neural crest cells establishes the structure of the central and peripheral nervous systems. In C. elegans, the bilateral Q neuroblasts and their descendants undergo long-range migrations with left/right asymmetry. QR and descendants on the right migrate anteriorly, and QL and descendants on the left migrate posteriorly, despite identical patterns of cell division, cell death, and neuronal generation. The initial direction of protrusion of the Q cells relies on the left/right asymmetric function of the transmembrane receptors UNC-40/DCC and PTP-3/LAR in the Q cells. Here we show that Q cell left/right asymmetry of migration is independent of the GPA-16/G pathway that regulates other left/right asymmetries including nervous system L/R asymmetry. No extracellular cue has been identified that guides initial Q anterior versus posterior migration. We show that the Collagens DPY-17 and SQT-3 control initial Q direction of protrusion. Genetic interactions with UNC-40/DCC and PTP-3/LAR suggest that DPY-17 and SQT-3 drive posterior migration and might act with both receptors or in a parallel pathway. Analysis of mutants in other Collagens and extracellular matrix components indicated that general perturbation of Collagens and the ECM did not result in directional defects, and that the effect of DPY-17 and SQT-3 on Q direction is specific. DPY-17 and SQT-3 are components of the cuticle, but a role in the basement membrane cannot be excluded. Possibly, DPY-17 and SQT-3 are part of a pattern in the cuticle and/or basement membrane that is oriented to the anterior-posterior axis of the animal and that is deciphered by the Q cells in a left-right asymmetric fashion. Alternatively, DPY-17 and SQT-3 might be involved in the production or stabilization of a guidance cue that directs Q migrations. In any case, these results describe a novel role for the DPY-17 and SQT-3 Collagens in directing posterior Q neuroblast migration. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY