FAK is linked to aggressive tumors, but its normal function is not clear. FAK knockdown early in Xenopus development anteriorizes the embryo via a loss of Wnt signaling. Wnt3a expression is FAK dependent in both embryos and human breast cancer cells, suggesting that a FAK–Wnt linkage is highly conserved.
Fibroblast growth factor (FGF) has been proposed to be involved in the specification and patterning of the developing vertebrate nervous system. There is conflicting evidence, however, concerning the requirement for FGF signaling in these processes. To provide insight into the signaling mechanisms that are important for neural induction and anterior-posterior neural patterning, we have employed the dominant negative Ras mutant, N17Ras, in addition to a truncated FGF receptor (XFD). Both N17Ras and XFD, when expressed in Xenopus laevis animal cap ectoderm, inhibit the ability of FGF to generate neural pattern. They also block induction of posterior neural tissue by XBF2 and XMeis3. However, neither XFD nor N17Ras inhibits noggin, neurogenin, or XBF2 induction of anterior neural markers. MAP kinase activation has been proposed to be necessary for neural induction, yet N17Ras inhibits the phosphorylation of MAP kinase that usually follows explantation of explants. In whole embryos, Ras-mediated FGF signaling is critical for the formation of posterior neural tissues but is dispensable for neural induction.
Protocadherin-18a (Pcdh18a) belongs to the delta 2-protocadherins, which constitute the largest subgroup within the cadherin superfamily. Here we present isolation of a full-length zebrafish cDNA that encodes a protein highly similar to human and mouse Pcdh18. Zebrafish pcdh18a is expressed in a complex and dynamic pattern in the nervous system from gastrula stages onward, with lesser expression in mesodermal derivatives. Pcdh18a-eGFP fusion protein is expressed in a punctate manner on the membranes between cells. Overexpression of pcdh18a in embryos caused cyclopia, mislocalization of hatching gland tissue, and duplication or splitting of the neural tube. Most neural markers tested were expressed in an approximately correct A-P pattern. By cell transplantation we showed that overexpression of pcdh18a causes diminished cell migration and reduced cell protrusions, resulting in a tendency of cells to stay more firmly aggregated, probably due to increased cell adhesion. In contrast, knockdown of pcdh18a by a morpholino oligonucleotide caused defects in epiboly, and led to reduced cell adhesion as shown by cell dissociation, sorting and transplantation experiments. These results suggest a role for Pcdh18a in cell adhesion, migration and behavior but not cell specification during gastrula and segmentation stages of development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.