We use Q neuroblasts in C. elegans to study neuronal cell migration. The QR and QL neuroblasts undergo initial protrusions anteriorly and posteriorly, respectively. They then migrate in the direction of protrusion and divide to produce three neurons, of which AQR (from QR) migrates anteriorly and PQR (from QL) posteriorly. Our results (Sundararajan and Lundquist, 2012) show that UNC-40/DCC acts in parallel to a pathway including MIG-21 and PTP-3/LAR in directing posterior migration of QR and QL. These proteins have left-right functional asymmetry. In QL, UNC-40 and PTP-3/MIG-21 act redundantly to direct posterior migration. In QR, UNC-40 and PTP-3/MIG-21 mutually inhibit each other's posterior migration and cause QR to migrate anteriorly. Hence, UNC-40, PTP-3 and MIG-21 contribute to signaling systems in QR and QL. We wanted to identify genes that function with UNC-40, PTP-3 and MIG-21 in QR and QL. In a forward genetic screen we identified
cdh-4, a fat-like cadherin implicated in Q descendant migration (Schmitz et al., 2008).
cdh-4 mutants show defects in QR and QL migration (75% of QR cells migrate posteriorly). To understand how
cdh-4 interacts with
unc-40,
ptp-3 and
mig-21, we built double mutants of
cdh-4 with these genes. In QR, both unc-40RNAi and ptp-3RNAi suppressed the posterior migration seen in
cdh-4 mutants, suggesting that this posterior migration requires functional UNC-40 and PTP-3. The above result shows that CDH-4 has a role in both UNC-40 and PTP-3 pathways, which might explain why
cdh-4 mutants show a high percentage of QR migrating posteriorly. However, in QL unc-40RNAi;
cdh-4 mutants show increased anterior migration, suggesting that UNC-40 and CDH-4 are required in redundant pathways for posterior QL migration. In contrast, ptp-3RNAi;
cdh-4 mutants resembled
cdh-4 mutants alone, suggesting that PTP-3 and CDH-4 might function in the same genetic pathway. Current studies are aimed at understanding the genetic interactions between
cdh-4 and
mig-21 and to identify whether CDH-4 acts in the Q cells or other cells. The
cdh-4 promoter driving GFP is not expressed in the Q cells. Cell specific RNAi techniques are being used to test autonomy of
cdh-4 function in Q descendant migration.