The cellular basis of cartilage growth and shape change in larval and metamorphosing Xenopus frogs

Abstract

As the first and sometimes only skeletal tissue to appear, cartilage plays a fundamental role in the development and evolution of vertebrate body shapes. This is especially true for amphibians whose largely cartilaginous feeding skeleton exhibits unparalleled ontogenetic and phylogenetic diversification as a consequence of metamorphosis. Fully understanding the evolutionary history, evolvability and regenerative potential of cartilage requires in-depth analysis of how chondrocytes drive growth and shape change. This study is a cell-level description of the larval growth and postembryonic shape change of major cartilages of the feeding skeleton of a metamorphosing amphibian. Histology and immunohistochemistry are used to describe and quantify patterns and trends in chondrocyte size, shape, division, death, and arrangement, and in percent matrix from hatchling to froglet for the lower jaw, hyoid and branchial arch cartilages of Xenopus laevis. The results are interpreted and integrated into programs of cell behaviors that account for the larval growth and histology, and metamorphic remodeling of each element. These programs provide a baseline for investigating hormone-mediated remodeling, cartilage regeneration, and intrinsic shape regulating mechanisms. These programs also contain four features not previously described in vertebrates: hypertrophied chondrocytes being rejuvenated by rapid cell cycling to a prechondrogenic size and shape; chondrocytes dividing and rearranging to reshape a cartilage; cartilage that lacks a perichondrium and grows at single-cell dimensions; and an adult cartilage forming de novo in the center of a resorbing larval one. Also, the unexpected superimposition of cell behaviors for shape change onto ones for larval growth and the unprecedented exploitation of very large and small cell sizes provide new directions for investigating the development and evolution of skeletal shape and metamorphic ontogenies.