Building a Co-ordinated Musculoskeletal System: The Plasticity of the Developing Skeleton in Response to Muscle Contractions

Murphy, Paula; Rolfe, Rebecca A.

doi:10.1007/978-3-031-38215-4_4

Cited by 7 publications

(1 citation statement)

References 167 publications

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“…These spatial re-arrangements involve multiple molecular and cellular interactions that are not well characterized. Spatial rearrangements are suspected to be driven by mechanical parameters, since modification of muscle contraction leads to significant defects in the musculoskeletal system formation [6], [7], [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Spatial and mechanical environments regulate the heterogeneity of myonuclei

Nicolas,

Bonnin,

Blavet

et al. 2024

Preprint

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Skeletal muscle formation involves tight interactions between muscle cells and associated connective tissue fibroblasts. Every muscle displays the same type of organisation, they are innervated in the middle and attached at both extremities to tendons. Myonuclei are heterogeneous along myotubes and regionalised according to these middle and tip domains. During development, as soon as myotubes are formed, myonuclei at muscle tips facing developing tendons display their own molecular program. In addition to molecular heterogeneity, a subset of tip myonuclei has a fibroblastic origin different to the classical somitic origin, highlighting a cellular heterogeneity of myonuclei in foetal myotubes. To gain insights on the functional relevance of myonucleus heterogeneity during limb development, we used 2D culture and co-culture systems to dissociate autonomous processes (occurring in 2D-cultures) from 3D-spatial environment of tissue development. We also assessed the role of mechanical parameters in myonucleus heterogeneity in paralysed limb muscles. The regionalisation of cellular heterogeneity was lost in 2D cell culture systems and paralyzed muscles. The molecular signature of MTJ myonuclei was also lost a dish and paralysed muscles indicating a requirement of spatial and mechanical input for MTJ formation. Tip genes that maintain their expression in a dish are involved in myofibrillogenesis and myotube attachments. The behaviour of regionalized markers in cultured myotubes and paralyzed muscles allows us to deduce whether the genes intervene in myogenesis, myotube attachment or MTJ formation.HighlightsThe regionalisation of cellular heterogeneity of myonuclei is lost in cultured myotubesBMP signalling regulates fibroblast nucleus incorporation into cultured myotubesThe molecular signature of MTJ myonuclei is lost in cultured myotubes and paralysed musclesTip genes involved in myofibrillogenesis maintain their regionalised expression in cultured myotubes

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Section: Introductionmentioning

confidence: 99%

Spatial and mechanical environments regulate the heterogeneity of myonuclei

Nicolas,

Bonnin,

Blavet

et al. 2024

Preprint

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Revisiting Old Questions With New Methods: The Effect of Embryonic Motility on Skull Development in the Domestic Chick

Watanabe,

Arqam,

Taylor

et al. 2024

Journal of Morphology

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Muscle loading is known to influence skeletal morphology. Therefore, modification of the biomechanical environment is expected to cause coordinated morphological changes to the bony and cartilaginous tissues. Understanding how this musculoskeletal coordination contributes to morphological variation has relevance to health sciences, developmental biology, and evolutionary biology. To investigate how muscle loading influences skeletal morphology, we replicate a classic in ovo embryology experiment in the domestic chick (Gallus gallus domesticus) while harnessing modern methodologies that allow us to quantify skeletal anatomy more precisely and in situ. We induced rigid muscle paralysis in developing chicks mid‐incubation, then compared the morphology of the cranium and mandible between immobilized and untreated embryos using microcomputed tomography and landmark‐based geometric morphometric methods. Like earlier studies, we found predictable differences in the size and shape of the cranium and mandible in paralyzed chicks. These differences were concentrated in areas known to experience high strains during feeding, including the jaw joint and jaw muscle attachment sites. These results highlight specific areas of the skull that appear to be mechanosensitive and suggest muscles that could produce the biomechanical stimuli necessary for normal hatchling morphology. Interestingly, these same areas correspond to areas that show the greatest disparity and fastest evolutionary rates across the avian diversity, which suggests that the musculoskeletal integration observed during development extends to macroevolutionary scales. Thus, selection and evolutionary changes to muscle physiology and architecture could generate large and predictable changes to skull morphology. Building upon previous work, the adoption of modern imaging and morphometric techniques allows richer characterization of musculoskeletal integration that empowers researchers to understand how tissue‐to‐tissue interactions contribute to overall phenotypic variation.

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