In a comprehensive study of nearly 400 tetrapod species, researchers at the RIKEN Center for Biosystems Dynamics Research have uncovered both expected and surprising patterns in how vertebrae are arranged along the spine—offering new insights into the role of Hox genes in shaping animal bodies.
While humans and giraffes both have seven neck vertebrae, birds vary widely, with necks composed of anywhere between nine and 25 bones. This variation reflects the broader differences in vertebral formulas—the number of vertebrae in each of the five regions of the spine (neck, rib cage, lower back, pelvis, and tail). For example, the standard human vertebral formula is 7, 12, 5, 5, 4.
Led by biophysicist Rory Cerbus, the RIKEN team sought to understand how these differences emerge among tetrapods, a group that includes mammals, reptiles, birds, and amphibians. Their investigation focused on the connection between vertebral formulas and Hox genes, which play a key role in body patterning across species and are remarkably conserved in evolution.
The researchers compiled the most extensive dataset to date on vertebral counts in tetrapods, including extinct species, through visits to museums, CT scans, and historical anatomical references. Using this database, they examined whether changes in vertebral numbers across species aligned with patterns seen in experimental alterations of Hox genes in lab animals.
In mammals, they found a clear pattern: when a vertebra is added to one spinal region, it is often lost from a neighboring one. This kind of compensatory shift reflects the kind of changes seen when Hox genes are experimentally perturbed in mice, supporting the idea that these genes help control vertebral segmentation in mammals.
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However, other tetrapod groups—such as birds and amphibians—did not consistently follow this rule. While Hox genes still appear to influence vertebral development in these animals, their role seems to operate through different mechanisms.
"We thought we might see a tidy picture where vertebrae simply shift between adjacent regions in all tetrapods," said Cerbus. "That turned out to be true for mammals, which suggests Hox genes are crucial for understanding their body plan. But the variation in birds and amphibians shows the picture is more complex."
Co-author Kyogo Kawaguchi adds that although Hox genes are clearly still active in shaping non-mammalian vertebrates, they may be used differently across evolutionary lineages. This complexity opens new directions for exploring how body plans evolved across the tree of life.