Fibroblast growth factor signalling controls successive cell behaviours during mesoderm layer formation in Drosophila

Abstract

SUMMARYFibroblast growth factor (FGF)-dependent epithelial-mesenchymal transitions and cell migration contribute to the establishment of germ layers in vertebrates and other animals, but a comprehensive demonstration of the cellular activities that FGF controls to mediate these events has not been provided for any system. The establishment of the Drosophila mesoderm layer from an epithelial primordium involves a transition to a mesenchymal state and the dispersal of cells away from the site of internalisation in a FGF-dependent fashion. We show here that FGF plays multiple roles at successive stages of mesoderm morphogenesis in Drosophila. It is first required for the mesoderm primordium to lose its epithelial polarity. An intimate, FGF-dependent contact is established and maintained between the germ layers through mesoderm cell protrusions. These protrusions extend deep into the underlying ectoderm epithelium and are associated with high levels of E-cadherin at the germ layer interface. Finally, FGF directs distinct hitherto unrecognised and partially redundant protrusive behaviours during later mesoderm spreading. Cells first move radially towards the ectoderm, and then switch to a dorsally directed movement across its surface. We show that both movements are important for layer formation and present evidence suggesting that they are controlled by genetically distinct mechanisms.

Cadherin switching during the formation and differentiation of theDrosophilamesoderm: implications for epithelial mesenchymal transitions

“…the mesectoderm and the adjacent ventral ectoderm), because the early Twist expression domain extends into this area. Like maternally provided E-cadherin in the wild-type embryo (Clark et al, 2011), the ectopically expressed E-cadherin ( Fig. 2F9) persists after the invaginated mesoderm has dispersed into individual cells.…”

“…However, although the transition from an epithelial tube to a cell layer occurred both in dof, stg and in dof, stg, twi-Gal4..E-cadherin embryos, the invaginated epithelial tube retained its epithelial structure and round crosssection for longer in the mutants than in the wild type ( Fig. 3A-C; see also Clark et al, 2011), and the establishment of contact between ectoderm and mesoderm was also delayed (supplementary material Fig. S2C-E).…”

“…In the absence of FGF, which is expressed in the ectoderm (Gryzik and Müller, 2004;Stathopoulos et al, 2004), the mesodermal cells fail to extend filopodia in the direction of the source of FGF (Clark et al, 2011). As soon as the mesoderm has invaginated, cell division occurs, with the rounding up of cells contributing to the dispersal of the mesoderm and the dissolution of adherens junctions.…”

“…Nonetheless, the mesodermal cells eventually spread out on the ectoderm (Clark et al, 2011). Thus, neither mitosis nor FGF signalling nor transcriptional downregulation of E-cadherin seem to be necessary to allow the mesodermal EMT.…”

Epithelial-mesenchymal transitions: insights from development

“…In invaginated mesodermal cells, the fibroblast growth factor (FGF) signaling components, Branchless (FGF), Htl (FGFR) and Stumps (Dof, FGFR-docker) are crucial for gastrulation (Beiman et al, 1996;Vincent et al, 1998;Stathopoulos et al, 2004; Kadam et al, 2009;Klingseisen et al, 2009). They cause flattening of mesodermal cells, the interaction of mesodermal cells with the underlying ectoderm and the dorsal migration of these cells following EMT, all of which are accompanied by a redistribution and progressive loss of E-cadherin-associated adherens junctions (McMahon et al, 2010;Clark et al, 2011). …”