title: Precise spatial restriction of BMP signaling is essential for articular cartilage differentiation.
abstract: The articular cartilage, which lines the joints of the limb skeleton, is distinct from the adjoining transient cartilage, and yet, it differentiates as a unique population within a contiguous cartilage element. Current literature suggests that articular cartilage and transient cartilage originate from different cell populations. Using a combination of lineage tracing and pulse-chase of actively proliferating chondrocytes, we here demonstrate that, similar to transient cartilage, embryonic articular cartilage cells also originate from the proliferating chondrocytes situated near the distal ends of skeletal anlagen. We show that nascent cartilage cells are capable of differentiating as articular or transient cartilage, depending on exposure to Wnt or BMP signaling, respectively. The spatial organization of the articular cartilage results from a band of Nog-expressing cells, which insulates these proliferating chondrocytes from BMP signaling and allows them to differentiate as articular cartilage under the influence of Wnt signaling emanating from the interzone. Through experiments conducted in both chick and mouse embryos we have developed a model explaining simultaneous growth and differentiation of transient and articular cartilage in juxtaposed domains.
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, U.P. 208016, India.
authors.forename: Ayan
authors.initials: A
authors.lastname: Ray
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, U.P. 208016, India.
authors.forename: Pratik Narendra Pratap
authors.initials: PN
authors.lastname: Singh
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Sohaskey
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Harland
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, U.P. 208016, India abandopa@iitk.ac.in.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Bandyopadhyay
mesh_terms: D000423:Alcian Blue; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D002642:Chick Embryo; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D000423:Alcian Blue; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D051153:Wnt Proteins; D000099176:Noggin Protein
keywords: Articular cartilage; BMP; Nog; Proliferating chondrocytes; Wnt