title: Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension.
abstract: Convergent extension driven by mediolateral intercalation of chondrocytes is a key process that contributes to skeletal growth and morphogenesis. While progress has been made in deciphering the molecular mechanism that underlies this process, the involvement of mechanical load exerted by muscle contraction in its regulation has not been studied. Using the zebrafish as a model system, we found abnormal pharyngeal cartilage morphology in both chemically and genetically paralyzed embryos, demonstrating the importance of muscle contraction for zebrafish skeletal development. The shortening of skeletal elements was accompanied by prominent changes in cell morphology and organization. While in control the cells were elongated, chondrocytes in paralyzed zebrafish were smaller and exhibited a more rounded shape, confirmed by a reduction in their length-to-width ratio. The typical columnar organization of cells was affected too, as chondrocytes in various skeletal elements exhibited abnormal stacking patterns, indicating aberrant intercalation. Finally, we demonstrate impaired chondrocyte intercalation in growth plates of muscle-less Sp(d) mouse embryos, implying the evolutionary conservation of muscle force regulation of this essential morphogenetic process.Our findings provide a new perspective on the regulatory interaction between muscle contraction and skeletal morphogenesis by uncovering the role of muscle-induced mechanical loads in regulating chondrocyte intercalation in two different vertebrate models.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, PO Box 26, Rehovot 76100, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shwartz
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Farkas
authors.forename: Tomer
authors.initials: T
authors.lastname: Stern
authors.forename: Attila
authors.initials: A
authors.lastname: Aszódi
authors.forename: Elazar
authors.initials: E
authors.lastname: Zelzer
mesh_terms: D000423:Alcian Blue; D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000196:embryology*; D002356:Cartilage / Q000033:anatomy & histology / Q000196:embryology*; D002465:Cell Movement / Q000502:physiology; D048430:Cell Shape; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D006132:Growth Plate / Q000196:embryology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D015233:Models, Statistical; D009119:Muscle Contraction / Q000502:physiology*; D009432:Neural Crest / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D010590:Phalloidine; D015027:Zebrafish
chemical_list: D010590:Phalloidine; D000423:Alcian Blue