Scientists at the Francis Crick Institute have made a groundbreaking advancement in developmental biology by creating human stem cell models that, for the first time, incorporate the notochord. This rod-shaped tissue plays a crucial role in guiding the formation of the spine and nervous system in developing embryos. The research, published on December 18 in Nature, marks a significant step forward in understanding how the human body forms during early stages of development.

The notochord is a defining feature of all vertebrates, serving as a structural guide in the developing body. It plays a key role in organizing tissues as the embryo grows, but due to its complexity, it has been notably absent in previous lab-grown models of human trunk development. This new breakthrough offers the potential to further our understanding of both normal and abnormal human development.

To create this model, the researchers first analyzed chicken embryos to understand how the notochord naturally forms. By combining this information with data from mouse and monkey embryos, they identified the precise timing and sequence of molecular signals needed to produce notochord tissue. Using this knowledge, they developed a carefully orchestrated series of chemical signals to induce human stem cells to form a notochord.

The stem cells generated a miniature “trunk-like” structure that spontaneously grew to a length of 1-2 millimeters. This structure contained developing neural tissue and bone stem cells, arranged in a way that mirrored the development observed in human embryos. The notochord’s role in guiding the formation of the spine and nervous system became evident as the cells organized themselves at the correct time and location.

The researchers believe this breakthrough could offer valuable insights into the study of birth defects affecting the spine and spinal cord. It could also advance our understanding of conditions related to the intervertebral discs, which develop from the notochord and can cause back pain when they degenerate with age.

James Briscoe, Group Leader of the Developmental Dynamics Laboratory and senior author of the study, commented: “The notochord acts like a GPS for the developing embryo, helping to establish the body’s main axis and guide the formation of the spine and nervous system. Until now, it’s been difficult to generate this vital tissue in the lab, limiting our ability to study human development and disorders. Now that we’ve created a working model, it opens doors to study developmental conditions that we’ve previously struggled to understand.”

Tiago Rito, Postdoctoral Fellow and first author of the study, added: “Finding the exact chemical signals to produce the notochord was like discovering the right recipe. Previous attempts to grow the notochord in the lab failed because we didn’t understand the precise timing of when to add the ingredients. What’s especially exciting is that the notochord in our lab-grown structures functions in much the same way as it would in a developing embryo. It sends out chemical signals that help organize surrounding tissue, just as it does during typical development.”

This pioneering work not only provides a new model for studying human development but also holds the potential for improving the understanding of spinal and neural disorders, ultimately leading to better treatments for conditions that affect millions of people worldwide.

By Impact Lab