Visualization of cartilage formation: insight into cellular properties of skeletal progenitors and chondrodysplasia syndromes.
The cellular events underlying skeletal morphogenesis and the formation of cartilage templates are largely unknown. We generated an imaging system to dynamically visualize limb mesenchymal cells undergoing successive phases in cartilage formation and to delineate the cellular function of key regulators of chondrogenesis found mutated in chondrodysplasia syndromes. We uncovered an unsuspected role for Sox9 in control of cell morphology, independent from its major downstream target ColIIa, critically required for the mesenchyme-to-chondrocyte transition. In contrast, Bmp signaling regulates a cellular program we term "compaction" in which mesenchymal cells acquire a cohesive cell behavior required to delineate the boundaries and size of cartilage elements. Moreover, we visualized labeled progenitor cells from different regions of the limb bud and identified unique cellular properties that may direct their contribution toward specific skeletal elements such as the humerus or digits. These findings shed light on the cellular basis for chondrodysplasia syndromes and formation of the vertebrate skeleton.
Barna
Maria
M
Molecular Biology Program, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA. mbarna@biochem.ucsf.edu
Niswander
Lee
L
D000818:Animals; D001755:Blastocyst / Q000378:metabolism / Q000648:ultrastructure; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism* / Q000648:ultrastructure; D002645:Chickens; D020219:Chondrogenesis; D024061:Collagen Type III / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics / Q000502:physiology; D018878:Limb Buds / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice / Q000196:embryology; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D024061:Collagen Type III; D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors