Unraveling the complex mysteries of embryonic beginnings

Magdalena (Magda) Cernica GoetzZernika-Goetz, who now studies developmental and stem cell biology at the University of Cambridge and the California Institute of Technology, recalls an artistic childhood where she loved to make things with her hands. In high school, she was fascinated by how the brain worked and planned to major in neuroscience, but when she saw a fetus for the first time as a college freshman, her aesthetic sense was sparked. “When you watch a fetus develop, you’re also fascinated by the mystery and magic of the process,” Zernika-Goetz explains. “I was interested in the beauty of it, but not just the beauty on the surface, but the beauty deep within it. How does this work?”

A chance encounter with the world of developmental biology led Zernica Götz to explore the secrets of the embryo, after which she completed her PhD at the University of Warsaw. Andrzej Tarkovsky She completed two postdoctoral fellowships before starting her own lab at the University of Cambridge in 1997. In 2019, she started a second lab group at Caltech. In both labs, she studies how stem cells differentiate and develop inside the embryo.

“I [at] “In my scientific journey, I study how cells become different from one another,” Zernica-Goetz said of her work. “I embrace those differences, no matter how small or large they are, because even small differences can lead to big differences.”

Tiny cells, big discoveries

As a new group leader, Zernika-Goetz investigated the impact of cell polarity on early embryonic development. The evidence at the time showed that mammalian embryos, namely mouse cells, Post-transplant.¹ However, mouse embryos Symmetric I challenged this notion before the transplant.² To determine whether this symmetry and subsequent cell polarity are linked, we required the ability to trace cell lineages.

Zernika-Goetz’s group is ready to solve that problem. Green fluorescent protein marker It is well suited for such tracking.³ Using this system, the research team demonstrated the existence of embryo polarity. Before transplant.^Four

“It was all fascinating,” he recalls. Carolina Nitsche“Magda was very excited, and she communicated this excitement to everyone in our group,” said Magda, director of the Mouse Transgenics and Gene Targeting Core at Emory University, who was then a postdoctoral researcher in the Zernica-Goetz lab.

This also challenged the view that the histological characteristics of the egg have no effect on embryo development, leading the team to investigate the effect of sperm penetration on mouse embryo development. In this regard, they The location of the first cleavage was determined.we also predicted the rate of cell division, since clones that inherited this position were more likely to divide first.^Five They then discovered that this early division clone later Inner cell mass Of the embryo.⁶

“This was very controversial,” Zernika-Goetz recalled, adding that some of her colleagues suggested she retract the study. “I didn’t. I knew it was morally wrong.”

“Some people said, ‘Well, we don’t think any of this is real.’ So she [few] “There were some tough times early on to establish myself,” she said. Tom Fleminga developmental biologist and professor emeritus at the University of Southampton. But he said she was well-regarded as a scientist even then. “When I looked at her papers, it made sense. It was logical. And I thought, ‘Oh, yeah, I wish I could do that.'”

Over time, as technology improved and scientists were able to probe deeper into the biology of embryos, other groups have replicated Zernika-Goetz’s results; recently, she found a similar cellular bias in two-cell embryos. Human fetus Similar to what she found in mice.⁷ Zernika-Goetz considers the project a career highlight, despite the frustrations it caused, but her favorite is one she started a decade later.

Building better embryo models

Techniques adapted from in vitro fertilization research allow scientists to culture and study mammalian embryos during the first few days of development, but after this period (day four in mice and day seven in humans), the embryo needs to implant in the uterus, at which point studying its development becomes exponentially more difficult.

Recognizing this limitation, Zernika-Goetz In vitro model of Post-transplant Mouse embryo development.^8,9 At the same time, she showed that pluripotent embryonic stem cells cultured on extracellular matrix proteins The structure formed It is comparable to the state of an embryo during implantation.^Ten Her group then took this approach Human fetus And human stem cells.¹¹

Following the discovery of self-organization in the embryo model, Zernika-Goetz refined the model to better mimic mammalian embryos. Her team used mouse embryonic stem cells to Trophoblast Stem CellsForms the placenta.¹² This combination better modeled the embryonic development and cell biology of the early embryo, but it did not allow for the recapitulation of key processes unique to the postimplantation embryo that rely on a third embryonic cell type.

To overcome this drawback, the team developed a model that incorporates embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm cells. By combining all three types of cells, Embryonic models The structure and developmental stage of the embryos closely resembled those of comparable mouse embryos.¹³ Expanding on this research, the team Human Embryo Model We follow a similar approach.¹⁴

“This journey started 10 years ago. It’s amazing. I never dreamed it would get this far, that it would be possible,” Zernika-Goetz said. “I’m so glad I didn’t give up.”

Share your passion for science

“Working with Magda was probably one of the best moments I can remember in my scientific research so far,” Nitsche said. She explained that Zernika-Götz was always available to discuss the data and was enthusiastic about the project. “She really makes people want to get involved and interested in this research.”

Its interests extend to explaining the world and science of embryos, and the book also weaves together Zernika-Goetz’s scientific journey as an immigrant and a woman scientist. “My goal was to write for people who really love science,” she said, adding that the book captures parts of science that aren’t expressed in published papers, including the joy of discovery and the day-to-day challenges.

Zernika-Goetz now runs two labs and has mentored more than 50 graduate students and postdoctoral fellows, many of whom have started their own research groups and remain close colleagues with Zernika-Goetz. “People have really benefited from working with her,” Fleming says.

“She was able to bring together all the different aspects of how an embryo develops and give it meaning,” Fleming said.

Zernika Getz I was nominated for this interview through an application for The Scientist’s Peer Profile Program.