A random cell motility gradient downstream of FGF controls elongation of an amniote embryo

Abstract

Most animal embryos grow through cell accumulation in a posterior growth zone, but the morphogenic forces that control the formation and directionality of the growth are unknown. Based on a study of axis elongation during formation of the trunk and tail structures in the chicken embryo, Bénazéraf et al. propose that tissue elongation in response to signalling mediated by fibroblast growth factor is a property emerging from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements. Most animal embryos grow through cell accumulation in a posterior growth zone, but the underlying forces are unknown. It is now proposed that posterior elongation in chicken embryos is an emergent property that arises from graded cell motility in random directions (as opposed to directed movement). This occurs in response to signalling through the fibroblast growth factor. Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient1, which has been implicated in the control of cell motility in this tissue2. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements.