Scientists at the Francis Crick Institute have generated human stem cell models1 which, for the first time, contain notochord — a tissue in the developing embryo that acts like a navigation system, directing cells where to build the spine and nervous system (the trunk).
The work, published today in Nature, marks a significant step forward in our ability to study how the human body takes shape during early development.
The notochord, a rod-shaped tissue, is a crucial part of the scaffold of the developing body. It is a defining feature of all animals with backbones and plays a critical role in organising the tissue in the developing embryo.
Despite its importance, the complexity of the structure has meant it has been missing in previous lab-grown models of human trunk development.
In this research, the scientists first analysed chicken embryos to understand exactly how the notochord forms naturally. By comparing this with existing published information from mouse and monkey embryos, they established the timing and sequence of the molecular signals needed to create notochord tissue.
With this blueprint, they produced a precise sequence of chemical signals and used this to coax human stem cells into forming a notochord.
The stem cells formed a miniature ‘trunk-like’ structure, which spontaneously elongated to 1-2 millimetres in length. It contained developing neural tissue and bone stem cells, arranged in a pattern that mirrors development in human embryos. This suggested that the notochord was encouraging cells to become the right type of tissue at the right place at the right time.
The scientists believe this work could help to study birth defects affecting the spine and spinal cord. It could also provide insight into conditions affecting the intervertebral discs — the shock-absorbing cushions between vertebrae that develop from the notochord. These discs can cause back pain when they degenerate with age.
James Briscoe, Group Leader of the Developmental Dynamics Laboratory, and senior author of the study, said: “The notochord acts like a GPS for the developing embryo, helping to establish the body’s main axis and guiding 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 model which works, this opens doors to study developmental conditions which we’ve been in the dark about.”
Tiago Rito, Postdoctoral Fellow in the Developmental Dynamics Laboratory, and first author of the study, said: “Finding the exact chemical signals to produce notochord was like finding the right recipe. Previous attempts to grow the notochord in the lab may have failed because we didn’t understand the required timing to add the ingredients.
“What’s particularly exciting is that the notochord in our lab-grown structures appears to function similarly to how it would in a developing embryo. It sends out chemical signals that help organise surrounding tissue, just as it would during typical development.”
