The Italian poet, Giovanni Pascoli, once said that inside all adults, there is a child, il fanciullino, who is responsible for putting each of us in contact with the world through imagination and sensitivity. My fanciullino was on steroids when I recently met at a school with second graders to talk about biology! There is nothing so satisfying as explaining biology to children. They have that uncanny curiosity that can light a fire under any adult’s lukewarm curiosity.
I started out by asking the children what is the most important day in one person’s life. Not surprisingly, their most popular answer was their birthday. After I rejected that answer and a string of others, I shocked them with my answer. I told them that it is okay to celebrate birthdays, but they should never forget to celebrate their Gastrulation Day! What??? they cried. It was the perfect opening for explaining early embryonic development.
It was developmental biologist Lewis Wolpert who wrote that, “It is not birth, marriage or death, but gastrulation, which is truly the most important time in your life.” Having spent infinite hours at the microscope studying embryonic development, I could not agree more. Gastrulation is a developmental stage, which in the human embryo starts at day 15 after fertilization and normally ends at day 21. In this fabulous stage, the whole body plan of the future organism is laid out, a grand ordering solemnly marked by the appearance of the primitive streak. At this point, we witness a complete rearrangement of the embryo, which is literally turned inside out as the third layer of cells, the mesoderm, forms between the endoderm and ectoderm. Every single organ in our body derives from one of these three layers of cells, which during gastrulation are migrating and being heavily rearranged.
The second grade took it well (you could hear a pin drop, a response unknown at my home when I’m explaining things). I told them that gastrulation is the most important time in our lives because a whole new genetic program starts, with so many genes becoming active and others being turned off. Cells need to turn off their glue proteins (adhesion molecules, to us geeks) in order to be able to migrate and move, I continued. Even the smallest error in this phase will result in an embryo that cannot develop further or is severely compromised. In my view, it is truly amazing that all this can happen.
As I left the second graders thinking about gastrulation day cakes, I thought to myself how this complex yet basic process has fascinated me all my scientific life. In 1924, Hilde Mangold, a student in the Hans Spemann laboratory, performed a stunning experiment. Working with salamander embryos during gastrulation, Mangold and Spemann took a small group of cells from a newt gastrula and transplanted them into the ventral side of another newt gastrula. The results were remarkable; the transplanted tissue developed into a second notochord (a tissue formed during gastrulation), inducing the formation of a second nervous system. The result was a two-headed tadpole! This group of cells is so powerful that they are known as the embryo or Spemann organizer. This is the power of cells during gastrulation. Happy gastrulation!
I have long been fascinated by these experiments, so one day, when I found myself on a Ph.D. Thesis committee in Utrecht, Netherlands. I visited the Hubrecht Laboratory, which keeps Hans Spemann’s original lab notebooks. I was able to hold his notebook in my hands, flick through the yellowed pages, and even take pictures, which I am glad to share on this page. Hans Spemann was awarded the Nobel Prize for Medicine and Physiology in 1935. Unfortunately, Hilde Mangold did not live long enough to receive the award, but her PhD thesis remains the foundation of modern molecular embryology. Happy gastrulation to you as well, Hilde!
Scientists have now elucidated most of the complex gene cascades involved in this process. If you want to learn more, I suggest reading this review — Lim J, Thiery JP (2012). Epithelial-mesenchymal transitions: insights from development. Development 139, 3471-3486. Recently, I read another article — Wyczalkowski MA, et al. (2012). Computational models for mechanics of morphogenesis. Birth Defects Res C Embryo Today 96, 132-152. —
which highlights the importance of biomechanical forces as the bridge connecting the cellular and genetic events to the tissue deformations that occur during gastrulation. The mechanics and the forces on cells, which need to bend and acquire new shape and positions during gastrulation, is a rather neglected area of study in embryonic development.
I think that mechanobiology is an area where cell biology will grow, given that we now have in our armamentarium tools such as in vivo fluorescence microscopy, laser ablation, and FRET, which allow studying physical cellular perturbation in vivo. Happy gastrulation, everyone!