The Q neuroblasts QR and QL are born in the same location along the longitudinal axis then migrate in opposite directions exposing QL but not QR to an EGL-20/Wnt signal. This Wnt signal induces expression of the homeobox transcription factor MAB-5/Hox, a determinant for posterior migration, causing the QL descendants (SDQL, PVM, and PQR) to migrate posteriorly.
mab-5 loss of function (lof) results in anterior migration of QL descendants, and
mab-5(
e1751), a gain of function (gof) allele that expresses MAB-5 in both QL and QR, results in posterior migration of QR descendants. To identify genes regulated by MAB-5 that drive posterior migration, RNA seq was conducted on wild-type,
mab-5lof, and
mab-5gof. Genes were found that were upregulated or downregulated in lof or gof backgrounds. Gene ontology term analysis showed that these were significantly enriched for genes encoding secreted and transmembrane molecules that mediate interactions with the extracellular matrix. We used RNAi to perturb genes that were upregulated in
mab-5gof and downregulated in
mab-5lof, with the idea that these might be genes that are upregulated by MAB-5 to drive posterior migration. We found that RNAi of approximately a third of these genes (17) modified posterior QR descendant AQR migration in
mab-5gof, indicating that they are required by MAB-5 to drive posterior migration. Existing mutations within genes were used to confirm RNAi results. The MAP kinase activated protein kinase
mak-1, and the C. elegans F-spondin homolog
spon-1 were both upregulated in
mab-5gof and both suppressed the
mab-5gof posterior AQR migration. Q cell specific RNAi experiments on these genes did not result in suppression, suggesting a non cell-autonomous role in posterior migration. A ChiP-seq study previously identified
mak-1 but not
spon-1 as a direct target of MAB-5 (Niu et al, 2011). The data taken together suggest that
mak-1 is a direct target of MAB-5 required for posterior migration of Q descendants, and
spon-1 may be indirectly controlled by MAB-5 in posterior migration.