Dataset Information

Common cellular origin and diverging developmental programs for different sesamoid bones.

ABSTRACT: Sesamoid bones are small auxiliary bones that form near joints and contribute to their stability and function. Thus far, providing a comprehensive developmental model or classification system for this highly diverse group of bones has been challenging. Here, we compare our previously reported mechanisms of patella development in the mouse with those of two anatomically different sesamoids, namely lateral fabella and digit sesamoids. We show that all three types of sesamoid bones originate from Sox9⁺ /Scx⁺ progenitors under the regulation of TGF? and independently of mechanical stimuli from muscles. Whereas BMP2 regulates the growth of all examined sesamoids, the differentiation of lateral fabella or digit sesamoids is regulated redundantly by BMP4 and BMP2. Next, we show that whereas patella and digit sesamoids initially form in juxtaposition to long bones, lateral fabella forms independently and at a distance. Finally, our evidence suggests that, unlike the synovial joint that separates patella from femur, digit sesamoids detach from the phalanx by formation of a fibrocartilaginous joint. These findings highlight both common and divergent molecular and mechanical features of sesamoid bone development, which underscores their evolutionary plasticity.

SUBMITTER: Eyal S

PROVIDER: S-EPMC6919532 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Common cellular origin and diverging developmental programs for different sesamoid bones.

Eyal Shai S Rubin Sarah S Krief Sharon S Levin Lihi L Zelzer Elazar E

Development (Cambridge, England) 20190228 4

Sesamoid bones are small auxiliary bones that form near joints and contribute to their stability and function. Thus far, providing a comprehensive developmental model or classification system for this highly diverse group of bones has been challenging. Here, we compare our previously reported mechanisms of patella development in the mouse with those of two anatomically different sesamoids, namely lateral fabella and digit sesamoids. We show that all three types of sesamoid bones originate from < ...[more]

PMID: 30745426

Similar Datasets

Project description:The fabella is a sesamoid bone located behind the lateral femoral condyle. It is common in non-human mammals, but the prevalence rates in humans vary from 3 to 87%. Here, we calculate the prevalence of the fabella in a Korean population and investigate possible temporal shifts in prevalence rate. A total of 52.83% of our individuals and 44.34% of our knees had fabellae detectable by computed tomography scanning. Men and women were equally likely to have a fabella, and bilateral cases (67.86%) were more common than unilateral ones (32.14%). Fabella presence was not correlated with height or age, although our sample did not include skeletally immature individuals. Our systematic review yielded 58 studies on fabella prevalence rate from 1875-2018 which met our inclusion criteria, one of which was an outlier. Intriguingly, a Bayesian mixed effects generalized linear model revealed a temporal shift in prevalence rates, with the median prevalence rate in 2000 (31.00%) being ~ 3.5 times higher than that in 1900 (7.64%). In all four countries with studies before and after 1960, higher rates were always found after 1960. Using data from two other systematic reviews, we found no increase in prevalence rates of 10 other sesamoid bones in the human body, indicating that the increase in fabella prevalence rate is unique. Fabella presence/absence is due to a combination of genetic and environmental factors: as the prevalence rates of other sesamoid bones have not changed in the last 100 years, we postulate the increase in fabella prevalence rate is due to an environmental factor. Namely, the global increase in human height and weight (due to improved nutrition) may have increased human tibial length and muscle mass. Increases in tibial length could lead to a larger moment arm acting on the knee and on the tendons crossing it. Coupled with the increased force from a larger gastrocnemius, this could produce the mechanical stimuli necessary to initiate fabella formation and/or ossification.

Project description:An important but largely unmet challenge in understanding the mechanisms that govern the formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic, and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from 12 genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasets--based on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genes--provisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true-positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides a substantially expanded framework for further studies of this model developmental system.

Project description:For successful growth and maintenance of primary myogenic cells in vitro, culture medium and addition of sera are the most important factors. At present it is not established as to what extent sera of different origin and composition, supplemented in media or serum-free media conditions influence myoblast function and responses to different stimuli. By assessing markers of proliferation, differentiation/fusion, quiescence, apoptosis and protein synthesis the aim of the current study was to elucidate how primary human myoblasts and myotubes are modulated by different commonly used serum using FCS (foetal calf serum), (CS-FCS charcoal-stripped FCS, a manufacturing process to remove hormones and growth factors from sera), HS (horse serum) as well as in serum free conditions (DMEM). To characterise the biological impact of the different serum, myoblasts were stimulated with Insulin (100 nM) and Vitamin D (100 nM; 1?,25(OH)2D3, 1?,25-Dihydroxycholecalciferol, Calcitriol), two factors with characterised effects on promoting fusion and protein synthesis or quiescence, respectively in human myoblasts/myotubes. We demonstrate that sera of different origin/formulation differentially affect myoblast proliferation and myotube protein synthesis. Importantly, we showed that quantifying the extent to which Insulin effects myoblasts in vitro is highly dependent upon serum addition and which type is present in the media. Upregulation of mRNA markers for myogenic fusion, Myogenin, with Insulin stimulation, relative to DMEM, appeared dampened at varying degrees with serum addition and effects on p70S6K phosphorylation as a marker of protein synthesis could not be identified unless serum was removed from media. We propose that these asymmetric molecular and biochemical responses in human myoblasts reflect the variable composition of mitogenic and anabolic factors in each of the sera. The results have implications for both the reproducibility and interpretation of results from experimental models in myoblast cells/myotubes.

Dataset Information

Common cellular origin and diverging developmental programs for different sesamoid bones.

Publications

Common cellular origin and diverging developmental programs for different sesamoid bones.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets