Endochondral ossification and the evolution of limb proportions

Wiley Interdiscip Rev Dev Biol. 2020 Jul;9(4):e373. doi: 10.1002/wdev.373. Epub 2020 Jan 29.


Mammals have remarkably diverse limb proportions hypothesized to have evolved adaptively in the context of locomotion and other behaviors. Mechanistically, evolutionary diversity in limb proportions is the result of differential limb bone growth. Longitudinal limb bone growth is driven by the process of endochondral ossification, under the control of the growth plates. In growth plates, chondrocytes undergo a tightly orchestrated life cycle of proliferation, matrix production, hypertrophy, and cell death/transdifferentiation. This life cycle is highly conserved, both among the long bones of an individual, and among homologous bones of distantly related taxa, leading to a finite number of complementary cell mechanisms that can generate heritable phenotype variation in limb bone size and shape. The most important of these mechanisms are chondrocyte population size in chondrogenesis and in individual growth plates, proliferation rates, and hypertrophic chondrocyte size. Comparative evidence in mammals and birds suggests the existence of developmental biases that favor evolutionary changes in some of these cellular mechanisms over others in driving limb allometry. Specifically, chondrocyte population size may evolve more readily in response to selection than hypertrophic chondrocyte size, and extreme hypertrophy may be a rarer evolutionary phenomenon associated with highly specialized modes of locomotion in mammals (e.g., powered flight, ricochetal bipedal hopping). Physical and physiological constraints at multiple levels of biological organization may also have influenced the cell developmental mechanisms that have evolved to produce the highly diverse limb proportions in extant mammals. This article is categorized under: Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Comparative Development and Evolution > Regulation of Organ Diversity Comparative Development and Evolution > Organ System Comparisons Between Species.

Keywords: chondrocytes; endochondral ossification; growth plates; limb proportions; skeletal allometry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution*
  • Body Patterning / physiology
  • Bone Development / physiology
  • Cell Differentiation
  • Cell Proliferation
  • Chondrocytes / cytology
  • Chondrocytes / physiology*
  • Chondrogenesis / physiology*
  • Embryo, Mammalian
  • Forelimb
  • Growth Plate / anatomy & histology
  • Growth Plate / cytology
  • Growth Plate / physiology*
  • Hindlimb
  • Locomotion / physiology
  • Mammals / anatomy & histology
  • Mammals / classification
  • Mammals / physiology*
  • Osteoblasts / cytology
  • Osteoblasts / physiology
  • Osteocytes / cytology
  • Osteocytes / physiology
  • Osteogenesis / physiology*