Talk:Musculoskeletal System - Shoulder Development
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Cite this page: Hill, M.A. (2024, April 27) Embryology Musculoskeletal System - Shoulder Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Musculoskeletal_System_-_Shoulder_Development |
2010
Commitment of chondrogenic precursors of the avian scapula takes place after epithelial-mesenchymal transition of the dermomyotome
BMC Dev Biol. 2010 Aug 31;10:91.
Wang B, Pu Q, De R, Patel K, Christ B, Wilting J, Huang R.
Department of Anatomy and Cell Biology, University of Goettingen, Kreuzbergring 36, 37075 Goettingen, Germany. baigang.wang@medizin.uni-goettingen.de Abstract BACKGROUND: Cells of the epithelially organised dermomyotome are traditionally believed to give rise to skeletal muscle and dermis. We have previously shown that the dermomyotome can undergo epithelial-mesenchymal transition (EMT) and give rise to chondrogenic cells, which go on to form the scapula blade in birds. At present we have little understanding regarding the issue of when the chondrogenic fate of dermomyotomal cells is determined. Using quail-chick grafting experiments, we investigated whether scapula precursor cells are committed to a chondrogenic fate while in an epithelial state or whether commitment is established after EMT.
RESULTS: We show that the hypaxial dermomyotome, which normally forms the scapula, does not generate cartilaginous tissue after it is grafted to the epaxial domain. In contrast engraftment of the epaxial dermomyotome to the hypaxial domain gives rise to scapula-like cartilage. However, the hypaxial sub-ectodermal mesenchyme (SEM), which originates from the hypaxial dermomyotome after EMT, generates cartilaginous elements in the epaxial domain, whereas in reciprocal grafting experiments, the epaxial SEM cannot form cartilage in the hypaxial domain.
CONCLUSIONS: We suggest that the epithelial cells of the dermomyotome are not committed to the chondrogenic lineage. Commitment to this lineage occurs after it has undergone EMT to form the sub-ectodermal mesenchyme.
PMID: 20807426
Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1
Development. 2010 Aug 1;137(15):2559-69.
Capellini TD, Vaccari G, Ferretti E, Fantini S, He M, Pellegrini M, Quintana L, Di Giacomo G, Sharpe J, Selleri L, Zappavigna V.
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. Abstract The genetic pathways underlying shoulder blade development are largely unknown, as gene networks controlling limb morphogenesis have limited influence on scapula formation. Analysis of mouse mutants for Pbx and Emx2 genes has suggested their potential roles in girdle development. In this study, by generating compound mutant mice, we examined the genetic control of scapula development by Pbx genes and their functional relationship with Emx2. Analyses of Pbx and Pbx1;Emx2 compound mutants revealed that Pbx genes share overlapping functions in shoulder development and that Pbx1 genetically interacts with Emx2 in this process. Here, we provide a biochemical basis for Pbx1;Emx2 genetic interaction by showing that Pbx1 and Emx2 can bind specific DNA sequences as heterodimers. Moreover, the expression of genes crucial for scapula development is altered in these mutants, indicating that Pbx genes act upstream of essential pathways for scapula formation. In particular, expression of Alx1, an effector of scapula blade patterning, is absent in all compound mutants. We demonstrate that Pbx1 and Emx2 bind in vivo to a conserved sequence upstream of Alx1 and cooperatively activate its transcription via this potential regulatory element. Our results establish an essential role for Pbx1 in genetic interactions with its family members and with Emx2 and delineate novel regulatory networks in shoulder girdle development.
PMID: 20627960
A Bayesian approach to age estimation in modern Americans from the clavicle
J Forensic Sci. 2010 May;55(3):571-83. Epub 2010 Apr 8.
Langley-Shirley N, Jantz RL.
Department of Anthropology, University of Tennessee, 250 South Stadium Hall, Knoxville, TN 37996, USA. nrshirley@gmail.com Abstract Clavicles from 1289 individuals from cohorts spanning the 20th century were scored with two scoring systems. Transition analysis and Bayesian statistics were used to obtain robust age ranges that are less sensitive to the effects of age mimicry and developmental outliers than age ranges obtained using a percentile approach. Observer error tests showed that a simple three-phase scoring system proved the least subjective, while retaining accuracy levels. Additionally, significant sexual dimorphism was detected in the onset of fusion, with women commencing fusion at least a year earlier than men (women transition to fusion at approximately 15 years of age and men at 16 years). Significant secular trends were apparent in the onset of skeletal maturation, with modern Americans transitioning to fusion approximately 4 years earlier than early 20th century Americans and 3.5 years earlier than Korean War era Americans. These results underscore the importance of using modern standards to estimate age in modern individuals.
PMID: 20384935 http://www.ncbi.nlm.nih.gov/pubmed/20384935
2009
Postnatal growth of the clavicle: birth to 18 years of age
J Pediatr Orthop. 2009 Dec;29(8):937-43.
McGraw MA, Mehlman CT, Lindsell CJ, Kirby CL.
Ohio University College of Osteopathic Medicine, Division of Pediatric Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. Abstract BACKGROUND: The purpose of our study was to perform a large cross-sectional study aimed at determining the postnatal growth pattern of the clavicle from birth to 18 years of age.
METHODS: We analyzed the digital chest radiographs of a convenience sample of 961 individuals between birth and 18 years of age. Malrotated radiographs were excluded. Right and left clavicle lengths were measured in millimeters from the most lateral ossified border to the most medial ossified border of each clavicle. Study patients were divided into 19 subgroups with the first group being labeled as "birth to 11 months of age" followed by 1-year-olds, 2-year olds, etc. Patients were also grouped by sex. There was a minimum of 25 patients in each group.
RESULTS: At 18 years of age the mean+/-SD clavicle length for females was 149+/-12 mm and for males it was 161+/-11 mm. Although a statistically significant difference (P=0.049) was noted between the length of right and left clavicles it was not clinically significant (0.036 mm). A steady growth rate was noted for both genders from birth to the age of 12 years (8.4 mm/y). Above the age of 12 years there were significant differences in the growth of the clavicles of girls (2.6 mm/y) versus boys (5.4 mm/y) (P<0.001). Our data suggest that females achieve 80% of their clavicle length by 9 years of age and boys by 12 years of age.
CONCLUSION: This cross-sectional study establishes that relatively little clavicle growth (20%) remains for girls beyond age 9 years and for boys beyond 12 years. The length of one clavicle may be properly judged by comparing it with the contralateral clavicle.
CLINICAL RELEVANCE: Remodeling of the clavicle shaft fractures is currently believed to be proportional to remaining growth. Our study questions the capacity of the clavicle to re-establish normal length beyond the age thresholds we have identified.
PMID: 19934713 http://www.ncbi.nlm.nih.gov/pubmed/19934713
A Runx2 threshold for the cleidocranial dysplasia phenotype
Hum Mol Genet. 2009 Feb 1;18(3):556-68. Epub 2008 Nov 20.
Lou Y, Javed A, Hussain S, Colby J, Frederick D, Pratap J, Xie R, Gaur T, van Wijnen AJ, Jones SN, Stein GS, Lian JB, Stein JL.
Department of Cell Biology, Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655-0106, USA.
Cleidocranial dysplasia (CCD) in humans is an autosomal-dominant skeletal disease that results from mutations in the bone-specific transcription factor RUNX2 (CBFA1/AML3). However, distinct RUNX2 mutations in CCD do not correlate with the severity of the disease. Here we generated a new mouse model with a hypomorphic Runx2 mutant allele (Runx2(neo7)), in which only part of the transcript is processed to full-length (wild-type) Runx2 mRNA. Homozygous Runx2(neo7/neo7) mice express a reduced level of wild-type Runx2 mRNA (55-70%) and protein. This mouse model allowed us to establish the minimal requirement of functional Runx2 for normal bone development. Runx2(neo7/neo7) mice have grossly normal skeletons with no abnormalities observed in the growth plate, but do exhibit developmental defects in calvaria and clavicles that persist through post-natal growth. Clavicle defects are caused by disrupted endochondral bone formation during embryogenesis. These hypomorphic mice have altered calvarial bone volume, as observed by histology and microCT imaging, and decreased expression of osteoblast marker genes. The bone phenotype of the heterozygous mice, which have 79-84% of wild-type Runx2 mRNA, is normal. These results show there is a critical gene dosage requirement of functional Runx2 for the formation of intramembranous bone tissues during embryogenesis. A decrease to 70% of wild-type Runx2 levels results in the CCD syndrome, whereas levels >79% produce a normal skeleton. Our findings suggest that the range of bone phenotypes in CCD patients is attributable to quantitative reduction in the functional activity of RUNX2.
PMID: 19028669 http://www.ncbi.nlm.nih.gov/pubmed/19028669
2007
Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development
J Cell Biol. 2007 Feb 26;176(5):709-18.
Ge C, Xiao G, Jiang D, Franceschi RT.
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA. Abstract The extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) pathway provides a major link between the cell surface and nucleus to control proliferation and differentiation. However, its in vivo role in skeletal development is unknown. A transgenic approach was used to establish a role for this pathway in bone. MAPK stimulation achieved by selective expression of constitutively active MAPK/ERK1 (MEK-SP) in osteoblasts accelerated in vitro differentiation of calvarial cells, as well as in vivo bone development, whereas dominant-negative MEK1 was inhibitory. The involvement of the RUNX2 transcription factor in this response was established in two ways: (a) RUNX2 phosphorylation and transcriptional activity were elevated in calvarial osteoblasts from TgMek-sp mice and reduced in cells from TgMek-dn mice, and (b) crossing TgMek-sp mice with Runx2+/- animals partially rescued the hypomorphic clavicles and undemineralized calvaria associated with Runx2 haploinsufficiency, whereas TgMek-dn; Runx2+/- mice had a more severe skeletal phenotype. This work establishes an important in vivo function for the ERK-MAPK pathway in bone that involves stimulation of RUNX2 phosphorylation and transcriptional activity.
PMID: 17325210 http://www.ncbi.nlm.nih.gov/pubmed/17325210
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064027
1993
Conversion of bone marrow in the humerus, sternum, and clavicle: changes with age on MR images
Radiology. 1993 Jul;188(1):159-64. Zawin JK, Jaramillo D.
Department of Radiology, Children's Hospital, Boston, MA 02115. Abstract To study the normal conversion of bone marrow in the humerus, sternum, and clavicle, 101 T1-weighted magnetic resonance (MR) studies obtained in 91 patients aged 2 days to 37 years were retrospectively evaluated. Conversion from hypointense (red) to hyperintense (yellow) bone marrow was assessed by comparison of signal intensity of the bone marrow with that of muscle and fat. Conversion began in the proximal humeral epiphysis (in 16 of 21 adequate studies [76%]), humeral diaphysis (17 of 30 adequate studies [57%]), and distal metaphysis (16 of 25 adequate studies [64%]) before age 1 year and was nearly complete in these regions (20 of 22 adequate studies [91%], 20 of 21 adequate studies [95%], and five of seven adequate studies [71%]) in examinations of children aged 1-5 years. In the proximal humeral metaphysis, conversion was seen in 21 of 22 adequate studies (95%) in children aged 1-5 years and was nearly complete in all by age 20 years. Conversion began in the sternum (six of six studies [100%] in children aged 6-10 years) and clavicle (six of eight studies [75%] in children aged 6-10 years) before age 11 years but was never complete. Bone marrow conversion in the humerus, sternum, and clavicle follows a well-defined pattern and is depicted earlier by MR imaging than one would expect on the basis of histologic data.
PMID: 8511291
