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# Biology# Developmental Biology

The Unique Development of Mammal Vertebrae

Research on jerboas reveals how vertebrae grow differently across species.

Kimberly L Cooper, C. J. Weber, A. J. Weitzel, A. Y. Liu, E. G. Gacasan, R. L. Sah

― 7 min read


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Table of Contents

Mammals show a wide variety of skeletal structures, especially when we look at their vertebrae. While many studies focus on the bones in the limbs and skulls, the spine also has unique features that differ from species to species. For example, humans, dolphins, and giraffes all have seven cervical vertebrae in their necks, but their neck lengths are very different. Buffalo have long neural spines on their thoracic vertebrae to support their heavy heads. Tails in mammals vary greatly, from the absence of a tail in some primates to long, grasping tails in certain monkeys. This raises the question: how do the differences in vertebral size and shape develop over time?

How Vertebrae Develop

Vertebrae come from different parts of the embryo. The skull forms from the neural crest and nearby tissue, limbs develop from buds that come from the lateral plate, and the vertebral skeleton arises from Somites. Research has shown how somites form, which are blocks of tissue in the trunk and tail. The rate at which these somites form is controlled by a molecular clock, and the number of somites determines the number of vertebrae an animal will have. Some species, like snakes, can have many vertebrae due to this process.

As somites develop, they gain specific identities based on their position in the body, which is controlled by Hox Genes. These genes are expressed in a specific order that corresponds to their arrangement in the genome. Hox genes help define different types of vertebrae, such as cervical (neck), thoracic (chest), lumbar (lower back), sacral (pelvic), and tail vertebrae. For instance, if Hox10 genes are not functioning correctly, lumbar vertebrae may become similar in shape to thoracic vertebrae, which would be unusual.

Once somites turn into the cartilage that will later become bone, less is known about how they gain their unique shapes and sizes. Each vertebra has a central part and various processes that create joints with adjacent vertebrae and provide attachment sites for muscles. While the basic shape of vertebrae is simple, their lengths can vary quite a bit, even among neighboring vertebrae.

Interestingly, the vertebral skeleton has a different evolutionary history than the limb skeleton, predating limb bones by at least 60 million years. Both vertebrae and limb bones grow through the same process called endochondral ossification. While we have learned a lot about how limb bones grow longer, much less is known about how vertebrae grow differently.

A Model for Study: The Lesser Egyptian Jerboa

To better understand these differences in skeletal growth, researchers are studying the lesser Egyptian jerboa. This animal walks on two legs and has longer hind limbs and feet compared to the more typical four-legged lab mice. The jerboa also has a notably long tail that is 1.5 times the length of a mouse tail when accounting for body size. Surprisingly, this long tail has fewer vertebrae than that of a mouse. The individual vertebrae in the jerboa's mid-tail are much longer, causing a significant difference in tail length compared to body size.

Through analysis of both jerboas and mice, researchers can look at how vertebrae grow over time. They track the growth of the tail and individual vertebrae from birth to maturity, focusing on when differences in length and proportions appear.

At birth, mouse and jerboa tails are about half the length of their bodies. However, by the time they are around three weeks old, the jerboa’s tail begins to grow much longer compared to its body size, while the mouse tail remains closer to the body length. This growth pattern continues until the jerboa reaches full adult proportions.

Cellular Growth in Tail Vertebrae

Vertebrae grow through endochondral ossification of their growth cartilages. To understand how growth rates differ in jerboa and mouse vertebrae, researchers focused on the vertebrae that showed the most and least growth. By labeling bone with a fluorescent dye, they can measure how quickly these growth cartilages elongate.

The study finds that in the mouse, growth in the first tail vertebra is slower than in the sixth vertebra. In contrast, the jerboa's first vertebra grows faster than its sixth. The jerboa’s tail vertebrae overall grow much quicker than those in mice. The height of growth cartilage helps indicate how fast these vertebrae can grow, with larger heights suggesting faster growth.

During this examination, researchers measured several aspects of the growth cartilages, such as their total height, the height of specific zones within the cartilage, and the size of Chondrocytes, which are cells involved in cartilage formation. They discovered that the jerboa’s tail vertebrae have taller growth zones, which suggests more cells are involved in the growth process, thus leading to a greater rate of growth.

In contrast, the size of the chondrocytes, which can influence overall growth speed, doesn't show large differences in the mouse. However, the jerboa's sixth vertebra has chondrocytes that are much larger than those found in the other vertebral growth cartilages, which contributes to its rapid elongation.

Molecular Mechanisms of Growth

In addition to studying how vertebrae grow, researchers are investigating the genetic factors that drive these differences. By comparing gene expressions between jerboas and mice, they can identify which genes are responsible for the unique growth patterns seen in the jerboa’s tail. These analyses reveal many genes that are involved in the processes of cartilage development and elongation.

Among the identified candidate genes, one key player is NPR3, which appears in various studies related to both limb and vertebral growth. NPR3 is involved in signaling pathways that help regulate growth rates. Interestingly, while NPR3 levels are higher in jerboas, it also plays a role in limiting excessive growth by regulating the activity of other signals involved in bone development.

To see how changes in NPR3 might affect tail growth, researchers created knockout mice that lack this gene. They observed that these mice had longer tails, indicating that NPR3 usually inhibits tail growth.

Summary of Findings

The observations drawn from studying both jerboas and mice provide valuable insights into how vertebrae grow and evolve. Differences in vertebral length and the number of vertebrae are not only determined by developmental processes but also influenced by genetic mechanisms. The study of jerboas sheds light on the cellular factors driving growth, while also highlighting significant genes that play roles in regulating these processes.

Overall, this research highlights the complexity of skeletal development in mammals, particularly in how vertebrae can achieve a variety of sizes and proportions. The findings suggest potential pathways for further investigation into how different species adapt their skeletal structures to meet their ecological needs. The work opens doors to understanding the genetic and cellular basis behind skeletal diversity, and its implications carry over into both evolutionary biology and potential applications in medicine.

With new techniques and models, researchers are better equipped to uncover the intricate details of how mammals develop their skeletons and the diversity that arises from these processes. This understanding not only enriches our knowledge of mammal biology but also can inform conservation efforts and the study of evolutionary adaptations.

Conclusion

The journey into understanding mammal skeletal diversity continues, revealing layers of complexity in the development and evolution of vertebrae. By examining species like the lesser Egyptian jerboa, scientists are able to explore the cellular and molecular foundations that contribute to the vast array of vertebral structures found in the animal kingdom today. The knowledge gained from such studies not only informs our understanding of mammalian evolution but also poses intriguing questions for future research in biology and genetics.

Original Source

Title: Cellular and molecular mechanisms that shape the development and evolution of tail vertebral proportion in mice and jerboas

Abstract: Despite the functional importance of the vertebral skeleton, little is known about how individual vertebrae elongate or achieve disproportionate lengths as in the giraffe neck. Rodent tails are an abundantly diverse and more tractable system to understand mechanisms of vertebral growth and proportion. In many rodents, disproportionately long mid-tail vertebrae form a crescendo-decrescendo of lengths in the tail series. In bipedal jerboas, these vertebrae grow exceptionally long such that the adult tail is 1.5x the length of a mouse tail, relative to body length, with four fewer vertebrae. How do vertebrae with the same regional identity elongate differently from their neighbors to establish and diversify adult proportion? Here, we find that vertebral lengths are largely determined by differences in growth cartilage height and the number of cells progressing through endochondral ossification. Hypertrophic chondrocyte size, a major contributor to differential elongation in mammal limb bones, differs only in the longest jerboa mid-tail vertebrae where they are exceptionally large. To uncover candidate molecular mechanisms of disproportionate vertebral growth, we performed intersectional RNA-Seq of mouse and jerboa tail vertebrae with similar and disproportionate elongation rates. Many regulators of posterior axial identity and endochondral elongation are disproportionately differentially expressed in jerboa vertebrae. Among these, the inhibitory natriuretic peptide receptor C (NPR3) appears in multiple studies of rodent and human skeletal proportion suggesting it refines local growth rates broadly in the skeleton and broadly in mammals. Consistent with this hypothesis, NPR3 loss of function mice have abnormal tail and limb proportions. Therefore, in addition to genetic components of the complex process of vertebral evolution, these studies reveal fundamental mechanisms of skeletal growth and proportion.

Authors: Kimberly L Cooper, C. J. Weber, A. J. Weitzel, A. Y. Liu, E. G. Gacasan, R. L. Sah

Last Update: 2024-10-26 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.10.25.620311

Source PDF: https://www.biorxiv.org/content/10.1101/2024.10.25.620311.full.pdf

Licence: https://creativecommons.org/licenses/by-nc/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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