WNT secreted glycoproteins and their putative receptors, the FRIZZLED (FZ) family of transmembrane proteins, function in a conserved signalling pathway to control many important developmental decisions. In C. elegans, the anteroposterior polarities of the B and T cells appear to be controlled by two WNT signals: LIN-44 and EGL-20. Mutations in
lin-17, which encodes a FZ-like protein, cause the loss of polarity in these cells, suggesting that LIN-17 is a receptor for these two WNT signals.
egl-20 and
lin-17 also control the migrations of QL descendents by regulating expression of the C. elegans HOX gene
mab-5 in the QL lineage. We have found that mutations in
egl-27 cause a loss of T cell polarity as well as cell migration defects reminiscent of
egl-20 and
lin-17 mutants.
egl-27 acts genetically upstream of
mab-5 in QL migrations, as do
egl-20 and
lin-17. Thus
egl-27 mutants show defects similar to those observed in two different Wnt mutants, suggesting that EGL-27 may function in both WNT pathways. We have cloned
egl-27 by microinjecting fragments of cosmid C04A2. The extents of rescuing fragments and the locations of molecular lesions associated with the
n170 and
mn553 alleles are consistent with an
egl-27 transcriptional unit containing both the C04A2.2 and C04A2.3 predicted genes. Database searches have revealed that the putative
egl-27 protien is is similar to the metastasis-associated factor Mta1, whose expression is elevated in rat and human metastasizing mammary adenocarcinoma cell lines. Thus EGL-27 appears to be a new component of the WNT signalling pathway in C. elegans and, given the similarity between EGL-27 and Mta1, perhaps in other species as well.