What is it about?

The mouth and throat skeletons of amphibians are comprised of a flexible network of cartilage parts whose shapes and arrangements vary widely among species, and undergo profound transformations in the metamorphosis from larva or tadpole to frog. Amphibian feeding cartilages thus represent an untapped opportunity to explore how cell behaviors contribute to developmental change and evolutionary innovation. This study is the first to describe and quantify the contributions of cell division, cell death, cartilage matrix accumulation, and changes in cell size and shape to the formation, growth and metamorphic shape change of cartilages for any amphibian or fish.

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Why is it important?

Cartilage develops earlier than bone, uses more cell behaviors than bone to grow, and forms the original template for most of the adult skeleton in vertebrate animals. Despite these differences, cartilage is largely overlooked in the developmental and evolutionary biology of skeleton. Biomedical research on cartilage is focused almost exclusively on the limb cartilages of mammals. Growth plate studies have entrenched the view that cartilages follow a stereotypical sequence of cell behaviors (division, matrix secretion, cell growth, and cell death) that plays out in discrete zones and precedes replacement by bone. Also, microCT studies have narrowed the study of skeletal evolution to mainly the bony skeletons of adults, and largely ignore the cartilage that precedes and prefigures the bone. This study reveals that the most commonly used lab amphibian, Xenopus laevis, utilizes multiple programs of cell behavior to grow its cranial cartilages and change their shape at metamorphosis. These programs contain four previously undescribed features that may be unique to frogs, and will be of great interest to evolutionary morphologists, cartilage biologists, and tissue regeneration experts. These are 1) cartilage cells growing to an exceptionally large cell size and then undergoing a phase of rapid cell division (what I call rejuvenation) that returns them to their predifferentiation size, shape, and state, 2) some rejuvenating cells forming an altogether new cartilage inside a dying larval one, 3) other rejuvenating cells changing the shape of a larval cartilage that stays fully differentiated, and 4) cartilages growing at single-cell dimensions and without a cartilage sheath (perichondrium) throughout larval life. More generally, the results provide a baseline and conceptual framework for evolutionary comparisons, and for investigating the cell communication-, biomechanics- and bioelectricity-based mechanisms involved in tissue growth, remodeling and shape regulation. The unprecedented use of rapid cell cycling to produce cartilage comprised of unusually large and small cells opens up new directions for investigating cartilage regeneration and cartilage pathologies like degenerative osteoarthritis.


This study demonstrates the potential for important and exciting cell-level discoveries using simple, student-friendly lab techniques (histology and immunohistochemistry) on a non-traditional lab organism. It also reinforces the importance of a "whole-animal, whole-life" perspective that is often missing in more reductionist, mechanism-based research programs.

Christopher Rose

Read the Original

This page is a summary of: The cellular basis of cartilage growth and shape change in larval and metamorphosing Xenopus frogs, PLoS ONE, January 2023, PLOS,
DOI: 10.1371/journal.pone.0277110.
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