Gastrulation generates three layers of cells (ectoderm, mesoderm, endoderm) from a single sheet, while large scale cell movements occur across the entire embryo. In amniote (reptiles, birds, mammals) embryos, the deep layers arise by epithelial-to-mesenchymal transition (EMT) at a morphologically stable midline structure, the primitive streak (PS). We know very little about how these events are controlled or how the PS is maintained despite its continuously changing cellular composition. Using the chick, we show that isolated EMT events and ingression of individual cells start well before gastrulation. A Nodal-dependent ‘community effect’ then concentrates and amplifies EMT by positive feedback to form the PS as a zone of massive cell ingression. Computer simulations show that a combination of local cell interactions (EMT and cell intercalation) is sufficient to explain PS formation and the associated complex movements globally across a large epithelial sheet, without the need to invoke long-range signalling.
A key process during the development of an embryo involves a single layer of cells reorganizing into three ‘germ layers’: the ectoderm, which becomes the skin and nervous system; the mesoderm, which gives rise to the skeleton, muscles and the circulatory and urinogenital systems, and the endoderm, which gives rise to the lining of the gut and associated organs. The process of forming these three layers is known as gastrulation.
To date most experiments on gastrulation in vertebrates have been performed on frog embryos. However, the embryos of amniotes, the group of ‘higher’ vertebrates that comprises reptiles, birds and mammals, differ from those of frogs in a number of ways. Now Voiculescu et al. have used a combination of experimental and computational techniques to shed new light on gastrulation in chick embryos.
Just prior to gastrulation, the cells of the amniote embryo are arranged in a flat disk, one cell thick, called the epiblast. The cells of the epiblast then move to form the mesoderm and endoderm (in a process called epithelial-to-mesenchymal transition). These cell movements also lead to the formation of a structure called the primitive streak that establishes the left-right symmetry of the organism, and also defines the midline of the body.
Now Voiculescu et al. have shown that the epithelial-to-mesenchymal transition starts before the primitive streak appears, and that two main processes drive gastrulation. One involves cells inserting themselves between other cells at the midline of the epiblast, which causes a double whorl-like movement within the plane of the epiblast. At the same time small numbers of cells leave the epiblast, and as these cells accumulate under the epiblast, they initiate a positive feedback effect by which they encourage more cells to leave the epiblast. Voiculescu et al. found that this ‘community effect’ involves signalling by a protein called Nodal. This protein effectively amplifies the epithelial-to-mesenchymal transition and leads to the appearance of the primitive streak at the midline.
Using computational modelling, Voiculescu et al. argue that the movements of gastrulation can be explained entirely based on local interactions between cells, without the need for cells to send signals over long distances to guide cell movements, as had been generally believed.