Zebrafish embryo with glowing spinal cord cells

Decoding the Spinal Cord: How Embryonic Cells Shape Our Nervous System

Soraya Malik in Science & Nature August 2025 • 4 min read.

"New research reveals the surprising ways early cells build the spinal cord, challenging long-held assumptions about development and growth."

The development of an embryo is a complex choreography where cells transform into distinct germ layers. For years, scientists believed that in mice, this process relies on neuromesodermal progenitors (NMPs), special stem cells that continue their work throughout the formation of the somites – precursors to vertebrae, ribs, and muscles.

However, the story gets more complex when we look at the rapidly developing zebrafish. Researchers have long debated whether zebrafish embryos rely on the same NMP-driven approach. Is there a self-renewal mechanism at play in these tiny fish, or does spinal cord development follow a different set of rules?

Now, a groundbreaking study has shed new light on this developmental puzzle. By tracing the lineages of early embryonic cells in zebrafish, scientists have uncovered a fascinating interplay between genetics and growth, revealing both conserved strategies and surprising species-specific adaptations in spinal cord formation.

Zebrafish Development: Challenging the Mouse Model

Zebrafish embryo with glowing spinal cord cells

In amniotes, cells continually allocate to the posterior pre-somitic mesoderm and spinal cord, but the existence of a similar mechanism in zebrafish has remained controversial. While studies have confirmed the presence of Sox2/Tbxta-positive cells in the tailbud, suggesting an NMP-like population, lineage analysis has presented conflicting results. Some argue against a stem cell-like population homologous to the mouse NMP pool.

To address this debate, researchers employed a genetic clone-tracing method called ScarTrace. By labeling early embryonic progenitors and tracking their descendants, they aimed to determine the precise timing of neural and mesodermal lineage restriction in zebrafish. The goal was to understand if these progenitors arise from a self-renewing stem cell pool, as they do in mouse embryos, or if an alternative mechanism is at play.

ScarTrace Experiment: Injected Cas9 RNA or protein with sgRNA into zebrafish embryos, creating unique 'scars' in the genome of labeled cells.
Distance Calculation: Isolated and sequenced scars from various adult fish tissues to determine the genetic distance between spinal cord, muscle, and other tissues.
Clustering Analysis: Heatmaps and bootstrapped trees revealed closer relationships between spinal cord and muscle tissues compared to spinal cord and anterior neural regions.

The findings suggest that spinal cord and paraxial mesoderm fates segregate during zebrafish embryogenesis through two possible models: continuous allocation and early segregation. To explore these segregation models, researchers conducted fate-mapping experiments using photolabelling to visualize the segregation, migration, and tissue contributions of mesoderm and ectoderm during zebrafish gastrulation.

A New Understanding of Spinal Cord Development

The team's detailed analysis revealed that zebrafish spinal cord development involves a combination of direct allocation during gastrulation and a delayed allocation from a tailbud NMP population. This challenges the traditional mouse model and highlights the diversity of strategies employed by different species to achieve the same developmental outcome. These results open new avenues for understanding the complex interplay between genetics, growth, and cellular dynamics in embryonic development.

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Everything You Need To Know

What are neuromesodermal progenitors (NMPs) and what role do they play in spinal cord development?

NMPs are specialized stem cells that are active during the formation of somites, which are precursors to vertebrae, ribs, and muscles. In mice, NMPs were thought to be key players throughout this process. However, research on zebrafish has challenged this view, revealing a more complex interplay of genetic factors and growth mechanisms in spinal cord formation. The study suggests that the role of NMPs and the strategies employed in spinal cord development can vary significantly between species, showcasing a diverse range of developmental approaches.

How does spinal cord development in zebrafish differ from that in mice?

The traditional understanding of spinal cord development comes from studying mice, where NMPs were thought to be central. However, in zebrafish, the process appears to be more complex. The research indicates that zebrafish spinal cord development involves both direct allocation during gastrulation and a delayed allocation from a tailbud NMP population. This contrasts with the mouse model and highlights the surprising species-specific adaptations involved in spinal cord formation. This difference suggests that while the end goal is the same, the pathways and mechanisms employed by different species can vary substantially.

What is ScarTrace and how was it used to study zebrafish spinal cord development?

ScarTrace is a genetic clone-tracing method used to understand the lineage of early embryonic cells. Researchers used it to label early embryonic progenitors in zebrafish and track their descendants to determine the timing of neural and mesodermal lineage restriction. The method involved injecting Cas9 RNA or protein with sgRNA into zebrafish embryos, which created unique 'scars' in the genome of labeled cells. The genetic distance between spinal cord, muscle, and other tissues was calculated by isolating and sequencing scars from adult fish tissues. By analyzing the relationships between spinal cord, muscle, and anterior neural regions, they could better understand the mechanisms behind spinal cord formation.

What insights did the ScarTrace experiment provide about the allocation of cells during zebrafish embryogenesis?

The findings suggest that spinal cord and paraxial mesoderm fates segregate during zebrafish embryogenesis through two possible models: continuous allocation and early segregation. The team's detailed analysis revealed that zebrafish spinal cord development involves a combination of direct allocation during gastrulation and a delayed allocation from a tailbud NMP population. This understanding challenges the traditional mouse model and offers a new perspective on how different species achieve spinal cord development.

How does this research change our understanding of embryonic development?

The research highlights the surprising diversity in the strategies different species use to build the spinal cord. The study challenges long-held assumptions, particularly those derived from the mouse model, by revealing that zebrafish employ a different developmental mechanism. The findings open new avenues for understanding the complex interplay between genetics, growth, and cellular dynamics. It emphasizes the importance of studying a variety of species to fully understand the intricacies of embryonic development and the adaptability of biological processes.