Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism of growth uncouples the lateral expansion of curved cartilaginous sheets from the control of cartilage thickness, a process which might be the evolutionary mechanism underlying adaptations of facial shape. In rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing limbs), the transverse integration of clonal columns determines the well-defined diameter and resulting rod-like morphology. We were able to alter cartilage shape by experimentally manipulating clonal geometries. Using in silico modeling, we discovered that anisotropic proliferation might explain cartilage bending and groove formation at the macro-scale.

Center for Brain Research Medical University Vienna Vienna Austria

Center for Regenerative Therapies Technische Universität Dresden Dresden Germany

Central European Institute of Technology Brno University of Technology Brno Czech Republic

Department of Biologic and Materials Sciences University of Michigan School of Dentistry Ann Arbor United States

Department of Genetics Cell Biology and Anatomy University of Nebraska Medical Center Omaha United States

Department of Histology and Embryology Medical Faculty Masaryk University Brno Czech Republic

Department of Information Technology Uppsala University Uppsala Sweden

Department of Medicine Karolinska Institutet Stockholm Sweden

Department of Neuroscience Karolinska Institutet Stockholm Sweden

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

Institute for Regenerative Medicine Sechenov 1st Moscow State Medical University Moscow Russia

John Innes Centre Norwich United Kingdom

National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda United States

Science for Life Laboratory Royal Institute of Technology Solna Sweden

Unit of Molecular Neurobiology Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden

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