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Elife. 2017 Apr 17;6. pii: e25902. doi: 10.7554/eLife.25902.

Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage.

Author information

1
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
2
Center for Brain Research, Medical University Vienna, Vienna, Austria.
3
Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
4
Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
5
Department of Information Technology, Uppsala University, Uppsala, Sweden.
6
Department of Histology and Embryology, Medical Faculty, Masaryk University, Brno, Czech Republic.
7
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
8
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
9
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, United States.
10
Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany.
11
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, United States.
12
Science for Life Laboratory, Royal Institute of Technology, Solna, Sweden.
13
John Innes Centre, Norwich, United Kingdom.
14
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, United States.
15
Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russia.

Abstract

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.

KEYWORDS:

BMP; GSalpha; Wnt/PCP; chondrocranium; developmental biology; facial cartilage growth; mathematical and material modelling; mouse; mouse mutants; scaling and shaping; stem cells

PMID:
28414273
PMCID:
PMC5417851
DOI:
10.7554/eLife.25902
[Indexed for MEDLINE]
Free PMC Article

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