WNT secreted glycoproteins and their putative receptors, the FRIZZLED (FZ) family of transmembrane proteins, function in a conserved signaling pathway to control many important developmental decisions. In C. elegans, the anteroposterior polarities of the B and T cells appear to be controlled by a WNT signal encoded by
lin-44. 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 the LIN-44 WNT signal. Components of the conserved WNT signaling pathway, including another WNT signal encoded by
egl-20,
lin-17, another FZ-like protein encoded by
mig-1, and a !-catenin-related protein encoded by
bar-1, also control the migrations of QL descendants 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. Furthermore, the expression of a
lin-44 reporter gene is not affected in
egl-27 mutants. Thus
egl-27 is not required for production of LIN-44. We have previously reported the cloning of
egl-27. The extents of rescuing fragments and the locations of molecular lesions associated mutant with alleles are consistent with an
egl-27 transcriptional unit of approximately 15kb. Northern blot analyses of wild-type and mutant mRNAs reveal three
egl-27 transcripts. The largest corresponds to the composite
egl-27 cDNA and is missing in the
n170 deletion mutant. The two smaller transcripts are present in each of the mutants and appear to be transcribed from start sites within the
egl-27 transcriptional unit. The
mn553 and
e2394 lesions map to the largest transcript suggesting that it encodes the EGL-27 protein that functions in cell polarity and cell migration. A transgene that fuses GFP in frame with EGL-27 is able to rescue
egl-27 mutants and appears to be expressed in all somatic nuclei from mid-embryogenesis through adulthood. This construct places GFP at the end of the coding region and is likely to tag proteins made from all three
egl-27 transcripts. Expression of a construct, designed to reflect the expression of the largest transcript only, changes during development and is observed in many, but not all, somatic cells. Mosaic analysis using the functional
egl-27::gfp transgene indicated that
egl-27 is required cell autonomously within the T cell for proper polarity, suggesting further that EGL-27 functions in the reception or transduction of WNT signals. Database searches have revealed that the amino-terminal half of the putative
egl-27 protein 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 signaling pathway in C. elegans and, given the similarity between EGL-27 and Mta1, perhaps in other species as well.