Muscle activity plays key role in joint formation
Questions over why joints fail to develop in embryos with paralysed limbs have been burning in the minds of many for a long time. An international team of researchers pieced together this puzzle and discovered the molecular mechanism responsible. The results are published in the journal Developmental Cell. The study sheds light on how muscle activity influences developing joints and explains how movement regulates a signalling pathway that is needed during a baby's developmental stage and beyond. According to the researchers, joint development relies on changes in gene expression that 'commit' cells to becoming part of the developing joint and set them apart from the surrounding cartilage tissue. Past studies have indicated that the Wnt/beta-catenin signalling pathway contributes significantly in sustaining this joint-cell 'fate' and ensuring that the joint cells do not differentiate into cartilage. The researchers from France, Israel and the US also found that muscle contraction contributes to skeletal formation. 'We have known for over a century that embryonic movement is intimately involved in development of joints,' explains Dr Elazar Zelzer from the Department of Molecular Genetics at Israel's Weizmann Institute of Science. 'However, the precise mechanism by which active musculature regulates joint formation has remained elusive,' the study's co-author added. According to the researchers, mouse models in which the animals were missing limb musculature or lacked muscle contractility showed disruptions in the normal process of joint formation. The cells at the 'presumptive joint sites stopped expressing classical joint markers and started following a pathway for the development of cartilage', the study reads. The findings suggest that the joint's formation failed because of the local loss of beta-catenin activity. 'Prior to the current study, the mechanisms that underlie the contribution of movement to the process of joint development were mostly missing,' Dr Zelzer commented. 'Our findings show that muscle contraction is necessary to maintain joint progenitor-cell fate and explain how and why movement-induced mechanical stimuli play a key role during development.' The results 'provide the missing link between progenitor-cell fate determination and embryonic movement, two processes shown to be essential for correct organogenesis', the study showed. Participating in the study were researchers from the French National Institute for Health and Medical Research (INSERM), the Paris-based Pierre and Marie Curie University, the French National Centre for Scientific Research (CNRS), the Hebrew University of Science in Israel and Stanford University of Medicine in the US.
Countries
France, Israel, United States