Molecular basis for skeletal variation: insights from developmental genetic studies in mice

Kappen, Claudia; Neubüser, Annette; Balling, Rudi; Finnell, Richard H.

doi:10.1002/bdrb.20136

Cited by 8 publications

(4 citation statements)

References 409 publications

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“…The morphogenesis of a vertebrate embryo skeleton follows an ordered progression of highly specific steps (Cancedda, Cancedda & Castagnola, ; Cancedda et al, ; Kappen et al, ). The construction of the skeletal elements takes place during endochondral bone formation, leading to the acquisition of their final form and shape (Kappen et al, ). In general, studies on the skeleton tend to focus on adult morphology (e.g.…”

Section: A Dynamic Model Of the Genesis Of New Skeletal Morphologiesmentioning

confidence: 99%

Sesamoids in tetrapods: the origin of new skeletal morphologies

et al. 2019

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Along with supernumerary bones, sesamoids, defined as any organized intratendinous/intraligamentous structure, including those composed of fibrocartilage, adjacent to an articulation or joint, have been frequently considered as enigmatic structures associated with the joints of the skeletal system of vertebrates. This review allows us to propose a dynamic model to account for part of skeletal phenotypic diversity: during evolution, sesamoids can become displaced, attaching to and detaching from the long bone epiphyses and diaphysis. Epiphyses, apophyses and detached sesamoids are able to transform into each other, contributing to the phenotypic variability of the tetrapod skeleton. This dynamic model is a new paradigm to delineate the contribution of sesamoids to skeletal diversity. Herein, we first present a historical approach to the study of sesamoids, discussing the genetic versus epigenetic theories of their genesis and growth. Second, we construct a dynamic model. Third, we present a summary of literature on sesamoids of the main groups of tetrapods, including veterinary and human clinical contributions, which are the best-studied aspects of sesamoids in recent decades. Finally, we discuss the identity of certain structures that have been labelled as sesamoids despite insufficient formal testing of homology. We also propose a new definition to help the identification of sesamoids in general. This review is particularly timely, given the recent increasing interest and research activity into the developmental biology and mechanics of sesamoids. With this updated and integrative discussion, we hope to pave the way to improve the understanding of sesamoid biology and evolution.

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Section: A Dynamic Model Of the Genesis Of New Skeletal Morphologiesmentioning

confidence: 99%

Sesamoids in tetrapods: the origin of new skeletal morphologies

et al. 2019

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“…Targeted deletion of individual Hox genes often affects patterning of those specific skeletal elements in whose precursor cells the respective transcript is highly expressed [2]. Altered cell differentiation as well as altered migration and adhesion have been postulated to be the cause of patterning abnormalities in the skeleton [3].…”

Section: Introductionmentioning

confidence: 99%

Morpholino-mediated knockdown in primary chondrocytes implicates Hoxc8 in regulation of cell cycle progression

Kamel¹,

Krüger²,

Kappen³

2009

Bone

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Numerous experiments in mutant and transgenic mice have implicated Hox transcription factors in development of the skeletal system, postulating a role for these proteins in cell proliferation of precursor cells and regulation of cell differentiation. Our own data from Hoxc8 and Hoxd4 transgenic mice suggest that Hoxc8 is involved in cell proliferation during cartilage development. In order to directly assess its role in cell proliferation of a specific skeletal cell type, the cartilage-producing chondrocyte, we performed morpholino-mediated knockdown experiments in normal primary chondrocytes. Through analysis of PCNA expression and staining for phosphorylated Histone 3, two cell cycle markers, we show that interference with Hoxc8 expression in chondrocytes reduces cell proliferation, but in the absence of apoptosis. Instead, cells with a knockdown in Hoxc8 expression appear to be delayed in their progression through the cell cycle. Our results provide evidence for prolonged duration of and delayed exit from M-phase, thus implicating a role for Hoxc8 in controlling cell cycle progression at this critical check point.

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“…Variance in the morphology of skeletal elements reflects a combination of factors, including genetic and environmental sources, as well as their interaction over the course of growth and development (Kappen et al, 2007). Establishing sources of variance is difficult given the nonlinear effects of developmental processes, which overlap with one another and build upon prior developmental stages (Hallgrímsson et al, 2009).…”

mentioning

confidence: 99%

Variation in human limb joint articular morphology

Horbaly,

Hubbe,

Sylvester

et al. 2023

American Journal of Biological Anthropology

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ObjectivesSynovial joints in human limbs strike a balance between mobility, stability, and articular fit, yet little is known about how these conflicting demands pattern intraspecific variation in articular shape. In this study, we use geometric morphometrics to establish the apportionment and magnitude of morphological variance of the articular surfaces of the human shoulder, elbow, hip, and knee. We hypothesize that variances will be comparable between articulating surfaces within a joint and will be larger in joints with smaller ranges of motion, given their plurality of functional demands.Materials and MethodsThree‐dimensional landmarks were taken on the articular surfaces of the glenohumeral, humeroulnar, acetabulofemoral, and tibiofemoral joints from CT scans of 200 skeletons from the University of Tennessee Donated Skeletal Collection (84 females, 116 males). Root mean‐squared distances between articulations calculated from Procrustes shape coordinates were used to determine variance distributions.ResultsWe found no difference in variances for each articular surface between the sexes or between left and right articular surfaces. A high range of motion is associated with greater morphological variance; however, this pattern is largely driven by the concave articular surfaces of each joint, which consistently exhibit statistically greater variance than their convex counterparts.DiscussionThe striking pattern of differential variance between articulating morphologies points to potential disparities in development between them. Consistently higher variance in concave surfaces may relate to chondral modeling theory for the formation of joints. Establishing intraspecific morphological variance patterns is a first step in understanding coordinated evolution among articular features.

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Molecular basis for skeletal variation: insights from developmental genetic studies in mice

Cited by 8 publications

References 409 publications

Sesamoids in tetrapods: the origin of new skeletal morphologies

Sesamoids in tetrapods: the origin of new skeletal morphologies

Morpholino-mediated knockdown in primary chondrocytes implicates Hoxc8 in regulation of cell cycle progression

Variation in human limb joint articular morphology

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