The development of an organism appears as a chaotic combination of signaling events, stochastic gene expression behaviors, and cell movements. However, if we take a closer look, these behaviors have an order. This fits into the general observation that embryogenesis is patterned, precise, and robust, despite the stochastic nature of microscopic processes. During early development, cells begin to organize into three germ layers (ectoderm, mesoderm, endoderm) concomitant with transforming a 2D sheet into a 3D structure – a process known as gastrulation. Reorganizing cells to generate such drastic changes in morphology requires mass cell movements. For instance, in avian embryos the cell migrations of gastrulation have characteristic whorl patterns, referred to as Polonaise movements. This is then followed by the timely ingression of cells into a structure known as the primitive streak (figure 1) (1).
Figure 1: Simplified schematic of Polonaise cell movements during avian gastrulation. Purple represents the primitive streak, the structure in which cells internalize to generate the layers of the embryo. Black arrows display the Polonaise patterns of cell movements. Left shows early gastrulation. Over time, the primitive streak grows and more cells ingress which is depicted on the right.
A question that arises from observing these organized cell movements is, how does a cell ‘know’ where to go? Intriguing as this question might be, it is perhaps not the right question to ask if we aim to understand how something as complex as an organism forms. Instead, it might be better to think about how embryos gradually and collectively build themselves and to rephrase the question to: ‘How are these collective cell movements controlled to form morphological structures that will carry out specific functions?’
Going back to avian gastrulation, it seems that cells are being carried along by a cellular crowd or flow of Polonaise movements. Furthermore, the rate of cell internalization increases at the primitive streak and the ingressed cells increase the likelihood that neighboring cells will also ingress – otherwise known as the community effect (2). This highlights that cells are part of large interacting collectives that together generate patterns and structures of the embryo. A perfect example of how a team can generate something much greater than the individuals themselves.
The question of how cells end up at their final destination is perhaps down to the same ‘luck’ of our conception and birth. Who we become as people largely depends on when and where we were born and thus which society we end up being influenced by. We are also bombarded with information from multiple sources which we need to make sense of and use in meaningful ways. During development, cells are regularly dividing, and they are influenced by their neighboring community of cells, the extracellular and mechanical environment, signaling events, and molecules inherited from the mother cell. In other words, a cell finds itself in a complex environment and it must integrate multiple sources of information to appropriately incorporate into the embryo and reach its final destination.
In addition to generating shape, cells must commit to their final fates in order to perform specialized functions. In early development, cells are pluripotent with the flexibility to become a wide range of cell types. Over developmental time, cells differentiate whereby they express a repertoire of genes and proteins which enable them to carry out specific functions. This early flexibility in cell fates is a good way to build an embryo; if cell fates were not flexible, and they were fated early on, it would be difficult for them to navigate to their final destination based on this early decided fate. Imagine trying to find your way through a dense crowd without the tools or influence to move people. Instead, cells are fated concomitantly with morphogenesis which allows the embryo to build itself robustly with minimal final errors.
The question of how cells ‘know’ where to go might better lend itself to later developmental processes when the embryo has developed more organized structures and cells are less flexible in their fate choices. One such example is the migration of neural crest cells in vertebrate embryos. Neural crest cells migrate long distances from the dorsal neural tube and give rise to multiple cell types such as bone, pigment cells in the skin, and neurons and glia in the nervous system (3). Still, neural crest cells migrate as a collective with contractions of rear cells driving the cells forward (4). Moreover, neural crest cells migrate between structures that have already been laid down in the embryo. In this context, where a cell will later reside depends on the neighboring cells, secreted signals, the mechanical environment, and the cell’s history (the prior events that have broadly specified them as neural crest cells).
By thinking about how cells find their destination, it is clear that the choreography of embryogenesis is governed by collective cell movements and early flexibility which suitably assigns appropriate cell fates during morphogenesis. After all, the embryo is building the parts whilst it is building the whole – a marvelous and intriguing characteristic of living systems.
1. Voiculescu, O., Bertocchini, F., Wolpert, L., Keller, R., and Stern, C. The amniote primitive streak is defined by epithelial cell intercalation before gastrulation. Nature 449, 1049–1052 (2007).
2. Voiculescu, O., Bodenstein, L., Lau, I-J., and Stern, C. Local cell interactions and self-amplifying individual cell ingression drive amniote gastrulation. eLife 2014;3:e01817 (2014).
3. Szabo, A., and Mayor, R. Mechanisms of neural crest cell migration. Annu. Rev. Genet. 52:43–63 (2018).
4. Shellard, A., Szabo, A., Trepat, X., and Mayor, R. Supracellular contraction at the rear of neural crest cell groups drives collective chemotaxis. Science 362, 339 (2018).
Header photograph taken by Ahmad Odeh https://unsplash.com/photos/ckm1yAe6jhU