Fig. 7. Models for the signalling events and cell movements during early mesoderm spreading. (A) Diagram of part of the invaginated mesodermal tube (light grey) and the underlying ectoderm (dark grey) showing a model of events during the establishment of contact between mesoderm and ectoderm. Left panel: FGF receptors on the mesodermal cell close to the ectoderm bind FGF secreted by the ectoderm (red dots), dimerise, undergo autophosphorylation and phosphorylate Dof (shown here as part of the receptor complex). However, FGF receptor activation alone is not sufficient to activate MAPK (dashed grey arrow) or lead to cell shape changes, either because it does not deliver a sufficiently strong signal or because of the presence of an inhibitor (Inhib.). It is postulated that an event at the cell surface (yellow star) is also needed that can only occur in the vicinity of the ectoderm and depends on FGF signalling, the Rho exchange factor Pebble and Rac GTPases. As a result of this event (right panel), the activation of MAPK becomes possible, either by suppression of the postulated inhibitor, or by strengthening the MAPK signalling pathway (large black arrow). Cell-shape changes ensue that bring the next cell into the vicinity of the ectoderm and allow it to undergo the same process. The requirement for the membrane event can be overridden by overexpression of FGF. (B) Diagram of the invaginated mesoderm before (left) and after (right) it has begun to spread. Depending on the mechanism by which cells move away from the site of invagination, the cells marked in red and yellow end up in different positions (right): (i) if the first mesodermal cells to make contact with the ectoderm (yellow) become the leading edge of a migrating cell sheet, these cells would end up in a more dorsal position than the cells starting at a position more distant from the ectoderm (red); and (ii) if cells that make contact with the ectoderm become stationary and other cells crawl over them, then the first cells to make contact with the ectoderm will remain near the site of invagination, while other mesodermal cells will end up in more dorsal positions.