Polarization and migration of neurons is essential during nervous system development. We use Q neuroblasts as a system to study neuronal cell migration. The QR and QL neuroblasts, born in the posterior lateral region of the worm, undergo initial polarizations at about one hour after hatching in the anterior and posterior directions respectively. They then migrate in the direction of protrusion and divide to produce three neurons of which AQR (from QR) migrates anteriorly to near the anterior deirid, and PQR (from QL) posteriorly to near the phasmid ganglia. Consistent with previous studies (Honigberg and Kenyon, 2000; Williams et al., 2003), we show that mutations affecting the transmembrane receptors UNC-40/DCC and PTP-3, a LAR type receptor tyrosine phosphatase, cause defects in direction of QR and QL polarization and migration. We found that UNC-40 and PTP-3 might act redundantly in directing posterior migration of QL, as defects were significantly more severe for QL in
ptp-3(
mu256);
unc-40(RNAi) than the single mutants alone. Furthermore, we show that loss of MIG-21, a small transmembrane protein with thrombospondin repeats (Williams 2003), caused near randomization of QL and QR protrusion and migration as previously observed. In an attempt to understand how these genes might be acting together in controlling Q cell migrations, we constructed double mutants of
mig-21 with
unc-40 and
ptp-3. Alone,
mig-21 mutants displayed many defects in QR anterior migration (QR often migrated posteriorly). Surprisingly, in
mig-21;
unc-40 double mutants, the defects in QR anterior migration were suppressed (QR migrated to the posterior), suggesting that posterior migration of QR in
mig-21 mutants required functional UNC-40. In contrast,
mig-21;
ptp-3 resembled
mig-21 alone for both QR and QL, suggesting that MIG-21 and PTP-3 might be working in the same pathway or in an independent pathway. Taken together, our data suggest that UNC-40 and PTP-3 might redundantly control posterior migration of QL. Furthermore, MIG-21 might normally inhibit UNC-40 in QR, such that in a
mig-21 mutant, UNC-40 drives posterior migration of QR. Current studies are directed at determining the focus of action of these genes.
unc-40 and
mig-21 have been reported to be expressed in QL and QR (Chan et al., 1996; Williams et al. 2003), and we have found that the
ptp-3B promoter is active in cells that are consistent with QL and QR, suggesting cell autonomous function. Furthermore,
unc-40(RNAi) driven in QL, QR, and the seam cells induces Q cell defects. We are using mosaic analysis to pinpoint where these genes are required.