Illustration of cell differentiation into spinal cord and muscle.

Decoding Spinal Cord Development: How Our Bodies Build Themselves

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Rhea Morgan in Science & Nature September 2025 • 5 min read.

"New research reveals that the spinal cord's growth is more adaptable and less rigid than previously thought, challenging long-held views in developmental biology and offering new insights into regenerative medicine."


The development of an embryo is an orchestrated dance of cells, each finding its place to form the complex structures of a living being. One of the most critical steps in this dance is the specification of cells into distinct germ layers, the foundation upon which all tissues and organs are built. In mammals, like mice, this process involves a population of stem cells known as neuromesodermal progenitors (NMps), which have the remarkable ability to become either spinal cord or mesoderm, the precursor to muscles and bones.

For years, scientists have been trying to understand how NMps contribute to the development of the spinal cord, especially in organisms like zebrafish, which develop at a rapid pace. New research is shedding light on the precise roles of these progenitors, revealing a surprising level of adaptability in the spinal cord's growth. This detailed understanding of NMps challenges previous assumptions and unlocks new avenues for regenerative medicine.

The latest study uses advanced genetic tracing techniques to observe individual cell lineages during spinal cord formation in zebrafish. By marking early embryonic progenitors, scientists have uncovered a strong connection between spinal cord and mesoderm tissues, suggesting a shared developmental origin. Live-imaging of cell lineages has revealed dynamic processes of cell allocation, suggesting the presence of both early and late segregating progenitor populations.

Unraveling the Secrets of Neuromesodermal Progenitors

Illustration of cell differentiation into spinal cord and muscle.

The central question addressed by this research is whether zebrafish NMps function as a conserved source of spinal cord tissue, and if so, to what extent they contribute to neural and mesodermal structures during development. The team employed a genetic clone-tracing method, ScarTrace, which uses CRISPR/Cas9 technology to label cells uniquely, allowing for the reconstruction of clonal relationships in a retrospective manner. This approach revealed that spinal cord tissues are more closely related to mesodermal derivatives, such as muscle, than to anterior neural derivatives like the brain.

The researchers discovered a closer clonal relationship between spinal cord and muscle when compared with spinal cord and anterior neural regions. This finding supports a model where NM lineage decisions occur at the foundation of spinal cord generation in zebrafish. Further tracing of lineage restriction, combining photo-labeling and single-cell tracking from an in toto light-sheet imaging dataset, demonstrated that this restriction happens during an early and direct segregation event with minimal amplification of the cellular pool.

  • Early Segregation: An initial population of NMps divides early in gastrulation, directly allocating cells to neural and mesodermal compartments.
  • Delayed Allocation: A second population in the tailbud undergoes delayed allocation, contributing to neural and mesodermal compartments only during late somitogenesis.
  • Mono-fated Progenitors: Cell tracking and retrospective cell fate assignment at late somitogenesis stages reveal a collection of mono-fated progenitors.
These observations support the presence of an NMp population that is a conserved source of spinal cord and paraxial mesoderm. However, the potential for self-renewal in vivo differs significantly from amniotes. While a population of bipotent progenitors exists in zebrafish, the degree to which individual cells divide and give rise to both cell fates remains limited. This implies that the lineage of NMps varies in a species-specific manner due to vastly different rates of differentiation and growth.

Implications for Regenerative Medicine

The new understanding of spinal cord development in zebrafish offers valuable insights for regenerative medicine. By identifying the specific populations of progenitors involved in spinal cord formation and their distinct lineage restrictions, researchers can explore strategies to manipulate these cells for therapeutic purposes. Understanding the factors that govern cell fate decisions and lineage allocation could pave the way for new treatments for spinal cord injuries and other neurological disorders.

About this Article -

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Everything You Need To Know

1

What are Neuromesodermal progenitors (NMps) and why are they important?

Neuromesodermal progenitors (NMps) are stem cells that play a vital role in early development. Specifically, they have the capacity to differentiate into either spinal cord tissue or mesoderm, which eventually forms muscles and bones. This dual potential makes them critical in forming the body's basic structure during embryogenesis.

2

What are genetic tracing techniques and why are they significant in studying spinal cord development?

Genetic tracing techniques, such as ScarTrace, are important because they allow scientists to follow individual cells and their descendants during development. By uniquely labeling cells using CRISPR/Cas9 technology, researchers can reconstruct cell relationships and understand how cells differentiate and contribute to various tissues, like the spinal cord and mesoderm. This method provides insights into developmental biology and regenerative medicine.

3

What do 'early segregation' and 'delayed allocation' mean in the context of spinal cord development?

Early segregation refers to the process where an initial population of Neuromesodermal progenitors (NMps) divides early during gastrulation. This division directly allocates cells to either neural or mesodermal compartments. Delayed allocation occurs when a second population of NMps in the tailbud contributes to neural and mesodermal compartments later, specifically during late somitogenesis. The timing of these allocations impacts the development of the spinal cord and adjacent tissues.

4

What are mono-fated progenitors and why are they important?

Mono-fated progenitors are cells that, by the late stages of somitogenesis, have committed to a specific fate; they will only develop into one type of cell, either neural or mesodermal. This commitment is crucial because it signifies the end of their ability to become multiple cell types and the beginning of their specialized role in forming specific tissues. Understanding how cells become mono-fated is vital for regenerative medicine, as it could inform strategies to direct cell differentiation for tissue repair.

5

What are the implications of understanding spinal cord development for regenerative medicine?

Understanding the development of the spinal cord through research on Neuromesodermal progenitors (NMps) has significant implications for regenerative medicine. By identifying the specific populations of progenitors involved in spinal cord formation and their lineage restrictions, researchers can explore strategies to manipulate these cells for therapeutic purposes. This knowledge could lead to new treatments for spinal cord injuries and other neurological disorders, aiming to repair or regenerate damaged tissue.

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