breaking symmetry --2/14/24

Today's selection -- from The Dance of Life by Magdalena Zernicka-Goetz and Roger Highfield. The quest by scientist Magdalena Zernicka-Goetz to understand the development of the embryo:

“The story of any new life is one of growth, development, and metamorphosis. A fertilized egg has an extraordinary capacity to divide into many cells that self-organize into a unique arrangement of matter, an embryo, which over time will make the human body. How do some cells within the early embryo become different from neighboring cells so that they make a body while the others form a placenta? The answer is symmetry breaking. 

“When symmetry is broken in the developing embryo, cells make choices: one starts to develop in one way and the other in another. Why? Which cell in an early embryo will give rise to the placenta? Which cell will pave the way for the baby itself? Human embryos have a yolk sac that helps nourish them, so which cell will give rise to the yolk sac within which the embryo proper will grow? 

“All of these decisions have to be made by the time the embryo implants. Each requires a symmetry-breaking event. 

“More symmetry-breaking events follow. For example, in the embryo proper, which cell will lead to the development of a head and which will make a heart? Where to put the top and where to put the bottom? How to tell right from left? What distinguishes back from front? Breaking an embryo's symmetry is one of the most influential processes in early life and central to the creation of the body plan. Most of my work has been devoted, in one way or another, to understanding when and how an embryo breaks its symmetry as a new life unfolds. I find it magical. 

“Collaboration and partnerships have helped me in this great quest. Around the turn of the millennium, Karolina Piotrowska came from Poland to join my team as a postdoctoral researcher. Karolina was extraordinarily gifted, having the embryonic equivalent of what successful gardeners in Britain call ‘green fingers’—perhaps they fluoresced with the glow of GFP—when it came to manipulating embryos. To get through a series of complex experiments required manual dexterity and lightness of touch. Karolina had those skills and she possessed the right mental attitude too when these fiddly experiments could easily go awry. 

“Most graduate students are shocked by the transition from being spoon-fed information during a degree course to working in a laboratory on real science, where manual dexterity becomes important and new skills have to be learned. Many people are surprised to discover that most newly designed experiments to determine new facts and to test new ideas simply don't go smoothly, at least not immediately—-getting all the conditions just right takes patience. Failure really is the order of the day when doing research. We have to learn from each failure so we can move forward. Karolina had the right blend of patience, grit, determination, and shining optimism to carry on when an experiment didn't produce anything useful, and to work until she was confident that experiments were run well, that all the controls indicated the results were not artifacts of the experiments themselves and were therefore credible. 

“The insights that would emerge from the work we did together led to my first paper being published in Nature. Because it was a prestigious journal, it was the first time that the work of my group would be truly noticed by my peers. Our work did indeed make a splash. But not in the way I intended. 

“Symmetry became the focus of an ugly dispute. If I look back at that period from a scientific point of view, it was perhaps the most difficult of my scientific life, and it seemed to drag on forever. John Gurdon provided vital friendship and support and warned me at the time that if we discovered something of true importance that went against the dogma of the day, it might take ten years to be confirmed and accepted by other groups and yet another decade to be appreciated. I would become another to suffer in the long struggle to understand the subtleties of symmetry. The episode would weigh heavily on me for years. 

“After Karolina arrived at Cambridge, we began with genesis, the big bang of development, the moment that sperm encounters egg. The latter is no ordinary cell but one that brims with potential, one that is uniquely equipped to create a new life. This is also a cell that can grow and divide to make history, record it, and change it too. 

“During the dance of life, the near-spherical fertilized egg undergoes tumultuous transformations as it cleaves and morphs. Cells in this early embryo undergo polarization, when one end of a developing cell accumulates a particular set of proteins (the PAR proteins I mentioned earlier) that makes it different from the other end. By the time the embryo implants in the mother, the first three significantly distinct tissues have formed from cells with different cellular fates. New axes form, such as those along the three mutually perpendicular dimensions of anterior-posterior (head-tail) axis, dorsal-ventral (back-belly) axis, and sinistro-dexter (left-right) axis. Nearly two decades after we did our study, it is still surprising how little we understand about how these cells decide their fates and how the axes are laid down, the earliest signs of these key changes, and how they shape our future destiny. 

“Other aspects of the first dance of life are less symmetrical than popular depictions. Many might think of eggs and sperm as equal partners in the creation of a new life. In one very important way—the contribution of genes from mother and father—they are. But that would be to do a huge disservice to the human egg, a cellular powerhouse of potential, transformation, and change.”



Magdalena Zernicka-Goetz, Roger Highfield


The Dance of Life: The New Science of How a Single Cell Becomes a Human Being


Basic Books


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