Neurons undergo long-range migration during development to reach their future positions, and they polarize towards the direction of movement. In C. elegans, descendants of the QL neuroblast migrate posteriorly, and those of the QR neuroblast migrate anteriorly. The Wnt EGL-20 drives expression of the Hox gene mab-5 in the QL, but not in the QR lineage, resulting in posterior migration of the QL descendants. By contrast, anterior migration of the QR lineage requires the activity of another Hox gene lin-39. How Wnt signaling interacts with these two Hox genes is not completely understood. We found that LIN-39 was expressed at high level in both the QL and the QR neuroblasts. Soon after the Q.a/p cells divided, LIN-39 was downregulated in the posteriorly-migrating QL.ap and the QL.pa cells, but remained high in the anterior-migrating QR.ap and the QR.pa cells. The level of LIN-39 in these cells seemed to correlate with the direction towards which these cells polarized. In the egl-20 or the mab-5 mutants, the QL descendants polarized and migrated towards the anterior, and LIN-39 level remained high in the QL.ap and the QL.pa cells. We found that mutations in the Wnt cwn-1 or the Frizzled mom-5 suppressed the anterior migration or polarization of the QL lineage, and the aberrantly high level of LIN-39 was also attenuated by the cwn-1 mutation. While cwn-1 promotes lin-39 expression in the QL lineage when the egl-20/mab-5 signaling was absent, LIN-39 level in the QR lineage was not affected by Wnts. As a result, mutations in cwn-1, egl-20 and lin-39 all affected QR anterior migration, and double mutants between any of these three mutations further worsened the phenotypes. We hypothesize that in the QL lineage, an egl-20-dependent MAB-5 represses LIN-39 transcription to allow for posterior polarization and migration of the QL.ap and the QL.pa cells. In the QR lineage, the Wnts and LIN-39 act in separate pathways to control QR anterior migration. This work is supported by the National Science Council, Taiwan (NSC100-2320-B-002-095-MY3) and National Taiwan University (NTU-CDP-102R7810).

Affiliations:
- Institute of Molecular Medicine, National Taiwan University, Taiwan
- Department of Molecular and Cell Biology, University of California, Berkeley, USA