Spinal cord nerve cells branching through the body resemble trees with limbs fanning out in every direction. But this image can also be used to tell the story of how these neurons, their jobs becoming more specialized over time, arose through developmental and evolutionary history. Researchers have traced the development of spinal cord neurons using genetic signatures and revealed how different subtypes of the cells may have evolved and ultimately function to regulate body movements.
The findings, published in the journal Science on April 23, 2021, offer researchers new ways of classifying and tagging subsets of spinal cord cells for further study, using genetic markers that differentiate branches of the cells’ family tree.
«A study like this provides the first molecular handles for scientists to go in and study the function of spinal cord neurons in a much more precise way than they ever have before,» says senior author of the study Samuel Pfaff, Salk Professor and the Benjamin H. Lewis Chair. «This also has implications for treating spinal cord injuries.»
Spinal neurons are responsible for transmitting messages between the spinal cord and the rest of the body. Researchers studying spinal neurons have typically classified the cells into «cardinal classes,» which describe where in the spinal cord each type of neuron first appears during fetal development. But, in an adult, neurons within any one cardinal class have varied functions and molecular characteristics. Studying small subsets of these cells to tease apart their diversity has been difficult. However, understanding these subset distinctions is crucial to helping researchers understand how the spinal cord neurons control movements and what goes awry in neurogenerative diseases or spinal cord injury.
«It’s been known for a long time that the cardinal classes, as useful as they are, are incomplete in describing the diversity of neurons in the spinal cord,» says Peter Osseward, a graduate student in the Pfaff lab and co-first author of the new paper, along with former graduate student Marito Hayashi, now a postdoctoral fellow at Harvard University.
Pfaff, Osseward and Hayashi turned to single-cell RNA sequencing technologies to analyze differences in what genes were being activated in almost 7,000 different spinal neurons from mice. They used this data to group cells into closely related clusters in the same way that scientists might group related organisms into a family tree.
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