Musculoskeletal System - Shoulder Development

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Stage20-23 limbs b.jpg

Introduction

Developing shoulder skeleton
Adult shoulder skeleton
Adult appendicular skeleton
Limb bud geometry and patterning[1]

The skeletal shoulder consists of: the clavicle (collarbone), the scapula (shoulder blade), and the humerus. Development of his region occurs through both forms of ossification processes.

The mesoderm forms nearly all the connective tissues of the musculoskeletal system. Each tissue (cartilage, bone, and muscle) goes through many different mechanisms of differentiation.

The musculoskeletal system consists of skeletal muscle, bone, and cartilage and is mainly mesoderm in origin with some neural crest contribution.

The intraembryonic mesoderm can be broken into paraxial, intermediate and lateral mesoderm relative to its midline position. During the 3rd week the paraxial mesoderm forms into "balls" of mesoderm paired either side of the neural groove, called somites.

Somites appear bilaterally as pairs at the same time and form earliest at the cranial (rostral,brain) end of the neural groove and add sequentially at the caudal end. This addition occurs so regularly that embryos are staged according to the number of somites that are present. Different regions of the somite differentiate into dermomyotome (dermal and muscle component) and sclerotome (forms vertebral column). An example of a specialized musculoskeletal structure can be seen in the development of the limbs.

Skeletal muscle forms by fusion of mononucleated myoblasts to form mutinucleated myotubes. Bone is formed through a lengthy process involving ossification of a cartilage formed from mesenchyme. Two main forms of ossification occur in different bones, intramembranous (eg skull) and endochondrial (eg limb long bones) ossification. Ossification continues postnatally, through puberty until mid 20s. Early ossification occurs at the ends of long bones.

Musculoskeletal and limb abnormalities are one of the largest groups of congenital abnormalities.


Historic Embryology: 1902 Shoulder Girdle
Musculoskeletal Links: Introduction | mesoderm | somitogenesis | limb | cartilage | bone | bone timeline | shoulder | pelvis | axial skeleton | skull | joint | skeletal muscle | muscle timeline | tendon | diaphragm | Lecture - Musculoskeletal | Lecture Movie | musculoskeletal abnormalities | limb abnormalities | developmental hip dysplasia | cartilage histology | bone histology | Skeletal Muscle Histology | Category:Musculoskeletal
Historic Musculoskeletal Embryology  
1853 Bone | 1885 Sphenoid | 1902 - Pubo-femoral Region | Spinal Column and Back | Body Segmentation | Cranium | Body Wall, Ribs, and Sternum | Limbs | 1901 - Limbs | 1902 - Arm Development | 1906 Human Embryo Ossification | 1906 Lower limb Nerves and Muscle | 1907 - Muscular System | Skeleton and Limbs | 1908 Vertebra | 1908 Cervical Vertebra | 1909 Mandible | 1910 - Skeleton and Connective Tissues | Muscular System | Coelom and Diaphragm | 1913 Clavicle | 1920 Clavicle | 1921 - External body form | Connective tissues and skeletal | Muscular | Diaphragm | 1929 Rat Somite | 1932 Pelvis | 1940 Synovial Joints | 1943 Human Embryonic, Fetal and Circumnatal Skeleton | 1947 Joints | 1949 Cartilage and Bone | 1957 Chondrification Hands and Feet | 1968 Knee

Some Recent Findings

  • Review - Genetics of scapula and pelvis development: An evolutionary perspective[2] "In tetrapods, the scapular and pelvic girdles perform the important function of anchoring the limbs to the trunk of the body and facilitating the movement of each appendage. This shared function, however, is one of relatively few similarities between the scapula and pelvis, which have significantly different morphologies, evolutionary histories, embryonic origins, and underlying genetic pathways. The scapula evolved in jawless fish prior to the pelvis, and its embryonic development is unique among bones in that it is derived from multiple progenitor cell populations, including the dermomyotome, somatopleure, and neural crest. Conversely, the pelvis evolved several million years later in jawed fish, and it develops from an embryonic somatopleuric cell population. The genetic networks controlling the formation of the pelvis and scapula also share similarities and differences, with a number of genes shaping only one or the other, while other gene products such as PBX transcription factors act as hierarchical developmental regulators of both girdle structures. Here, we provide a detailed review of the cellular processes and genetic networks underlying pelvis and scapula formation in tetrapods, while also highlighting unanswered questions about girdle evolution and development."
  • Congenital Anatomical Variant of the Clavicle[3] "The aim of this study is to present a rare abnormality of the clavicle (Code: SGS01) that was discovered in an ossuary in the Church of San Gaetano (Sulmona, central Italy; XVII-XIX centuries CE). In the middle third, the clavicle had three areas with losses of substance in the form of oval-shaped foramina with maximum diameters of 1-2 cm that were located in the anterior and superior surfaces of the diaphysis. The margins of these foramina were well defined and rounded, and the surfaces of the canal walls were smooth. Additionally, there were no zones of bony activity or reactive changes around the foramina. This new congenital anomaly of the clavicle and blood vessels is consistent with a variant that might have originated during fetal growth in which the subclavian vein or artery remained included during the process of ossification of the clavicle."
  • Developmental origin of the clavicle, and its implications for the evolution of the neck and the paired appendages in vertebrates[4] "In fish, the pectoral appendage is adjacent to the head, but during vertebrate evolution a long neck region emerged via caudal relocation of the pectoral appendage. The pectoral appendage is comprised of endochondral portions, such as the humerus and the scapula, and a dermal portion, such as the clavicle, that contributes to the shoulder girdle. In the search for clues to the mechanism of the caudal relocation of the pectoral appendage, the cell lineage of the rostral lateral plate mesoderm was analyzed in chickens. It was found that, despite the long neck region in chickens, the origin of the clavicle attached to the head mesoderm ranged between 1 and 14 somite levels. Because the pectoral limb bud and the endochondral pectoral appendage developed on 15-20 and 15-24 somite levels, respectively, the clavicle-forming region corresponds to the embryonic neck, which suggests that the relocation would have been executed by the expansion of the source of the clavicle. The rostral portion of the clavicle-forming region overlaps the source of the cucullaris muscle, embraces the pharyngeal arches caudally, and can be experimentally replaced with the head mesoderm to form the cucullaris muscle, which implies that the mesodermal portion could have been the head mesoderm and that the clavicle would have developed at the head/trunk boundary. The link between the head mesoderm and the presumptive clavicle appears to have been the developmental constraint needed to create the evolutionarily conserved musculoskeletal connectivities characterizing the gnathostome neck. In this sense, the dermal girdle of the ganathostomes would represent the wall of the branchial chamber into which the endochondral pectoral appendage appears to have attached since its appearance in evolution."
  • Development of the shoulder girdle musculature[5] "The muscles of the shoulder region are important for movements of the upper limbs and for stabilizing the girdle elements by connecting them to the trunk. They have a triple embryonic origin. First, the branchiomeric shoulder girdle muscles (sternocleidomastoideus and trapezius muscles) develop from the occipital lateral plate mesoderm using Tbx1 over the course of this development. The second population of cells constitutes the superficial shoulder girdle muscles (pectoral and latissimus dorsi muscles), which are derived from the wing premuscle mass. This muscle group undergoes a two-step development, referred to as the "in-out" mechanism. Myogenic precursor cells first migrate anterogradely into the wing bud. Subsequently, they migrate in a retrograde manner from the wing premuscle mass to the trunk. SDF-1/CXCR4 signaling is involved in this outward migration. A third group of shoulder muscles are the rhomboidei and serratus anterior muscles, which are referred to as deep shoulder girdle muscles; they are thought to be derived from the myotomes. It is, however, not clear how myotome cells make contact to the scapula to form these two muscles. In this review, we discuss the development of the shoulder girdle muscle in relation to the different muscle groups."
More recent papers  
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Search term: Shoulder Development | Scapula Development | Clavicle Development

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1[6] "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."

Textbooks

  • The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 15 the skeletal system
  • Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 11 Limb Dev (bone not well covered in this textbook)
  • Before we Are Born (5th ed.) Moore and Persaud Chapter 16,17: p379-397, 399-405
  • Essentials of Human Embryology Larson Chapter 11 p207-228

Timeline

Shoulder Development Timeline
Carnegie Stage Event
17 chondrogenic progenitor of the humerus and the medial border of the scapula can be observed.
18 chondrogenic progenitor for rest of the scapula appears.
19 glenohumeral joint will begin delaminating and showing a looser central band (interzone). Denser lateral bands will join the humeral head (caput humeri) and the margins of the articular surface of the scapula, thus forming the glenoid labrum (glenoid ligament).
21 long head of the biceps tendon present
22 glenoid labrum (glenoid ligament) present
23 coracohumeral ligament present
Week
Fetal Week 10 osteogenic process begins in the humeral head. Primitive glenohumeral ligament present
Fetal Week 11 osteogenic process begins in the scapula
Links: shoulder | joint | limb | timeline     Data from human histological study.[7]
Table Of Ossification Of The Bones Of The Shoulder
Bone Centres Time of appearance of centre Union of primary and secondary centres; remarks.
Clavicle Diaphysis 6th week There are two centres in the shaft, a medial and a lateral. These blend on the 45th day (Mall). Shaft and epiphysis unite between the 20th and 25th years.
Sternal epiphysis 18th to 20th year
Scapula Primary centres: The chief centre appears near the lateral angle. The subcoracoid centre appears at the base of the coracoid process and also gives rise to a part of the superior margin of the glenoid fossa. The coracoid process joins the body about the age of puberty. The acromial epiphysis centres (two or three in number) fuse with one another soon after their appearance and with the spine between the 22nd and 25th years (Quain); 20th year (Wilms). The subcoracoid and the epiphysis of the coracoid process, the glenoid fossa, the inferior angle, and the vertebral margin join between the 18th and 24th years in the order mentioned (Sappey).
1. That of the body, the spine, and the base of the glenoid cavity. 8th week (Mall) 1
2. Goraooid process 1st year
3. Subcoracoid 10th to 12th year
Epiphyses:
Acromial epiphyses 15th to 18th year
Epiphysis of the inferior angle. 16 to 18th year
Epiphyses of the vertebral border. 18th to 20th year
Epiphyses of upper surface of coracoid. 16th to 18th year.
Epiphysis of surface of glenoid fossa. 16th to 18th year.
Links: limb | bone | upper limb ossification timeline | lower limb ossification timeline | Historic - Chapter 11 Development of the Skeleton | timeline | Category:Timeline     Table Data Reference[8]


Acromial secondary ossification centers began appear at age 10 and clavicular ones, while uncommon, began forming at age 11. Fusion of acromial primary and secondary ossification centers began at age 14 and was generally complete after age 16.[9] A similar time course has been shown in Japanese subjects.[10]


Links: upper limb ossification timeline

Embryonic Shoulder

Human embryonic shoulder girdle 01.jpg Drawing of a model of the right shoulder girdle of the 17mm. (Robinson) embryo, viewed from behind.Human embryonic shoulder girdle (17mm CRL)[11]

The sternal segment (S.S.) has been cut coronally to expose the interior, and the acromial segment has been cut horizontally for the same purpose.

The black area in each is bone, the dotted area surrounding the bone is precartilage, and the area surrounding this is perichondrium.

Above the junction of the two segments, two circles and a black dot are seen; the circles represent supraclavicular nerves, the black dot represents the cephalic vein.

The scapula has been purposely shortened.

Legend

  • Ac. pr. - acromion process
  • A. S. - acromial segment of clavicle
  • C. Al. - clei-do-mastoid
  • C. Cl. I. - coraco-clavicular ligament
  • C. pr. - coracoid process
  • T. - trapezius muscle
  • P.M. - pectoralis major
  • St. MI. - sterno-miastoid
  • S. S. - sternal segment of clavicle
Human embryonic shoulder girdle (17mm CRL)[11] 17mm CRL (Robinson) embryo
  • Week 7 - difficult to estimate the amount of shrinkage in this historic material.
  • Stage 18 CRL 13 - 17 (Somites 44 - 48)
  • Stage 19 CRL 16 - 18 (Somites 48 - 51)

Myogenesis

  • Early myogenic progenitor cells in the dermomyotome can be initially identified by the transcription factor Pax3.
  • Subsequent myogenic program development then depends on the myogenic determination factors (Myf5, MyoD, and MRF4), both Myf5 and MyoD are expressed in the limbs.
  • Final differentiation of these cells into post-mitotic muscle fibers in the limb bud is regulated by another myogenic determination factor, Myogenin.

Some text modified from[12]

Links: Muscle Development

Limb Bone

Limb sox9 and Wnt6 expression[13]
Chicken- limb bud chondrogenesis

Bone formation within the limb occurs by endochondral ossification of a pre-existing cartilage template. Ossification then replaces the existing cartilage except in the regions of articulation, where cartilage remains on the surface of the bone within the joint. Therefore bone development in the limb is initially about cartilage development or chondrogenesis.

In addition, there are two quite separate aspects to this development.

  1. Pattern - where the specific regions will commence to form cartilage, which will be different for each cartilage element.
  2. Chondrogenesis - the differentiation of mesoderm to form cartilage, which will be essentially the same program for all cartilage templates.

A recent study has identified that the overlying limb surface ectoderm potentially inhibits limb early chondrogenesis through Wnt6 signaling.[13]


Links: Cartilage Development | Bone Development

Clavicle Development

(collarbone)

Postnatal Growth

A paper has characterised the postnatal growth of male and female clavicles (data shown below).[14]

  • 18 years of age the mean clavicle length +/-SD for females was 149+/-12 mm and for males it was 161+/-11 mm.
  • 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).
  • Females achieve 80% of their clavicle length by 9 years of age and boys by 12 years of age.

Scapula Development

(shoulder blade)

Humerus Development

Pelvis

Hip bone

The skeletal pelvis consists of: the sacrum and coccyx (axial skeleton), and pelvic girdle formed by a pair of hip bones (appendicular skeleton). Before puberty, he pelvic girdle also consists of three unfused bones: the ilium, ischium, and pubis. In chicken, the entire pelvic girdle originates from the somatopleure mesoderm (somite levels 26 to 35) and the ilium, but not of the pubis and ischium, depends on somitic and ectodermal signals.[15]


Links: Pelvis Development

Molecular

Fibroblast Growth Factors

  • Fgf8 - morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.[16]

T-box Transcription Factors

References

  1. Kicheva A & Briscoe J. (2010). Limbs made to measure. PLoS Biol. , 8, e1000421. PMID: 20644713 DOI.
  2. Young M, Selleri L & Capellini TD. (2019). Genetics of scapula and pelvis development: An evolutionary perspective. Curr. Top. Dev. Biol. , 132, 311-349. PMID: 30797513 DOI.
  3. Viciano J, Urbani V & D'Anastasio R. (2017). Congenital Anatomical Variant of the Clavicle. Anat Rec (Hoboken) , 300, 1401-1408. PMID: 28296289 DOI.
  4. Nagashima H, Sugahara F, Watanabe K, Shibata M, Chiba A & Sato N. (2016). Developmental origin of the clavicle, and its implications for the evolution of the neck and the paired appendages in vertebrates. J. Anat. , 229, 536-48. PMID: 27279028 DOI.
  5. Pu Q, Huang R & Brand-Saberi B. (2016). Development of the shoulder girdle musculature. Dev. Dyn. , 245, 342-50. PMID: 26676088 DOI.
  6. Capellini TD, Vaccari G, Ferretti E, Fantini S, He M, Pellegrini M, Quintana L, Di Giacomo G, Sharpe J, Selleri L & Zappavigna V. (2010). Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1. Development , 137, 2559-69. PMID: 20627960 DOI.
  7. Hita-Contreras F, Sánchez-Montesinos I, Martínez-Amat A, Cruz-Díaz D, Barranco RJ & Roda O. (2018). Development of the human shoulder joint during the embryonic and early fetal stages: anatomical considerations for clinical practice. J. Anat. , 232, 422-430. PMID: 29193070 DOI.
  8. Keibel F. and Mall FP. Manual of Human Embryology I. (1910) J. B. Lippincott Company, Philadelphia.
  9. Kothary P & Rosenberg ZS. (2015). Skeletal developmental patterns in the acromial process and distal clavicle as observed by MRI. Skeletal Radiol. , 44, 207-15. PMID: 25319561 DOI.
  10. Fujii K, Takeda Y & Miyatake K. (2015). Development of secondary ossification centres of the acromion in Japanese youth: a computed tomographic study. J Orthop Surg (Hong Kong) , 23, 229-32. PMID: 26321557 DOI.
  11. 11.0 11.1 Fawcett. (1913). The Development and Ossification of the Human Clavicle. J Anat Physiol , 47, 225-34. PMID: 17232952
  12. Giordani J, Bajard L, Demignon J, Daubas P, Buckingham M & Maire P. (2007). Six proteins regulate the activation of Myf5 expression in embryonic mouse limbs. Proc. Natl. Acad. Sci. U.S.A. , 104, 11310-5. PMID: 17592144 DOI.
  13. 13.0 13.1 Geetha-Loganathan P, Nimmagadda S, Christ B, Huang R & Scaal M. (2010). Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo. BMC Dev. Biol. , 10, 32. PMID: 20334703 DOI.
  14. McGraw MA, Mehlman CT, Lindsell CJ & Kirby CL. (2009). Postnatal growth of the clavicle: birth to 18 years of age. J Pediatr Orthop , 29, 937-43. PMID: 19934713 DOI.
  15. Malashichev Y, Christ B & Pröls F. (2008). Avian pelvis originates from lateral plate mesoderm and its development requires signals from both ectoderm and paraxial mesoderm. Cell Tissue Res. , 331, 595-604. PMID: 18087724 DOI.
  16. Yu SR, Burkhardt M, Nowak M, Ries J, Petrásek Z, Scholpp S, Schwille P & Brand M. (2009). Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules. Nature , 461, 533-6. PMID: 19741606 DOI.


Reviews

Huang R, Christ B & Patel K. (2006). Regulation of scapula development. Anat. Embryol. , 211 Suppl 1, 65-71. PMID: 17006658 DOI.

Hall BK. (2001). Development of the clavicles in birds and mammals. J. Exp. Zool. , 289, 153-61. PMID: 11170011

Klima M. (1987). Early development of the shoulder girdle and sternum in marsupials (Mammalia: Metatheria). Adv Anat Embryol Cell Biol , 109, 1-91. PMID: 3324657

Articles

Currarino G & Herring JA. (2009). Congenital pseudarthrosis of the clavicle. Pediatr Radiol , 39, 1343-9. PMID: 19763557 DOI.

Kreitner KF, Schweden F, Schild HH, Riepert T & Nafe B. (1997). [Computerized tomography of the epiphyseal union of the medial clavicle: an auxiliary method of age determination during adolescence and the 3d decade of life?]. Rofo , 166, 481-6. PMID: 9272998 DOI.

Ogden JA, Conlogue GJ & Bronson ML. (1979). Radiology of postnatal skeletal development. III. The clavicle. Skeletal Radiol. , 4, 196-203. PMID: 531584

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Cite this page: Hill, M.A. (2019, December 14) Embryology Musculoskeletal System - Shoulder Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Shoulder_Development

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