The major molecular pathways involve members of the Wnt, Notch, BMP, FGF8 and GATA families.
Activation of FGF by two ligands that function together, FGF4 and FGF8 (17) in Xenopus and FGF8 and FGF24 in zebrafish (18), is necessary for mesoderm formation.
FGF8 is implicated in the process of this dispersal from the primitive streak.
This FGF10 expression stimulates WNT3 expression in the above ectodermal cells – resulting in formation of the apical ectodermal ridge (AER) as well as inducing FGF8 expression.
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#When Shh normally secreted from the ZPA is inhibited (either through use of tamoxifen or Shh-null mutants) the AER morphology, particularly its anterior extent, is perturbed and its FGF8 signaling decreased.
Activation of various secreted factors (Vg1, Nodal, Wnt8C, FGF8 and Chordin) and transcription factors (Brachyury and Goosecoid) adjacent to the site of streak formation is required for this process.
FGF8 |
Secreated anosmin-1 enhances FGF activity by promoting FGF8-FGFR1 complex formation, whereas inhibits both BMP5 and WNT3A activities.
Also induces the mesenchymal cells to secrete FGF10, which acts through WNT3A to sustain the AER’s expression of FGF8.