Human shoulder development is adapted to obstetrical constraints.

In humans, obstetrical difficulties arise from the large head and broad shoulders of the neonate relative to the maternal birth canal. Various characteristics of human cranial development, such as the relatively small head of neonates compared with adults and the delayed fusion of the metopic suture, have been suggested to reflect developmental adaptations to obstetrical constraints. On the other hand, it remains unknown whether the shoulders of humans also exhibit developmental features reflecting obstetrical adaptation. Here we address this question by tracking the development of shoulder width from fetal to adult stages in humans, chimpanzees, and Japanese macaques. Compared with nonhuman primates, shoulder development in humans follows a different trajectory, exhibiting reduced growth relative to trunk length before birth and enhanced growth after birth. This indicates that the perinatal developmental characteristics of the shoulders likely evolved to ease obstetrical difficulties such as shoulder dystocia in humans.

Development of the shoulder girdle musculature.

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.

Expansion of the neck reconstituted the shoulder-diaphragm in amniote evolution.

The neck acquired flexibility through modifications of the head-trunk interface in vertebrate evolution. Although developmental programs for the neck musculoskeletal system have attracted the attention of evolutionary developmental biologists, how the heart, shoulder and surrounding tissues are modified during development has remained unclear. Here we show, through observation of the lateral plate mesoderm at cranial somite levels in chicken-quail chimeras, that the deep part of the lateral body wall is moved concomitant with the caudal transposition of the heart, resulting in the infolding of the expanded cervical lateral body wall into the thorax. Judging from the brachial plexus pattern, an equivalent infolding also appears to take place in mammalian and turtle embryos. In mammals, this infolding process is particularly important because it separates the diaphragm from the shoulder muscle mass. In turtles, the expansion of the cervical lateral body wall affects morphogenesis of the shoulder. Our findings highlight the cellular expansion in developing amniote necks that incidentally brought about the novel adaptive traits.

On the homology of the shoulder girdle in turtles.

The shoulder girdle in turtles is encapsulated in the shell and has a triradiate morphology. Due to its unique configuration among amniotes, many theories have been proposed about the skeletal identities of the projections for the past two centuries. Although the dorsal ramus represents the scapular blade, the ventral two rami remain uncertain. In particular, the ventrorostral process has been compared to a clavicle, an acromion, and a procoracoid based on its morphology, its connectivity to the rest of the skeleton and to muscles, as well as with its ossification center, cell lineage, and gene expression. In making these comparisons, the shoulder girdle skeleton of anurans has often been used as a reference. This review traces the history of the debate on the homology of the shoulder girdle in turtles. And based on the integrative aspects of developmental biology, comparative morphology, and paleontology, we suggest acromion and procoracoid identities for the two ventral processes.

Evaluation of fetal anthropometric measures to predict the risk for shoulder dystocia.

OBJECTIVE: To evaluate the quality of anthropometric measures to improve the prediction of shoulder dystocia by combining different sonographic biometric parameters. METHODS: This was a retrospective cohort study of 12,794 vaginal deliveries with complete sonographic biometry data obtained within 7 days before delivery. Receiver-operating characteristics (ROC) curves of various combinations of the biometric parameters, namely, biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference, abdominal diameter (AD), abdominal circumference (AC) and femur length were analyzed. The influences of independent risk factors were calculated and their combination used in a predictive model. RESULTS: The incidence of shoulder dystocia was 1.14%. Different combinations of sonographic parameters showed comparable ROC curves without advantage for a particular combination. The difference between AD and BPD (AD - BPD) (area under the curve (AUC) = 0.704) revealed a significant increase in risk (odds ratio (OR) 7.6 (95% CI 4.2-13.9), sensitivity 8.2%, specificity 98.8%) at a suggested cut-off ≥ 2.6 cm. However, the positive predictive value (PPV) was low (7.5%). The AC as a single parameter (AUC = 0.732) with a cut-off ≥ 35 cm performed worse (OR 4.6 (95% CI 3.3-6.5), PPV 2.6%). BPD/OFD (a surrogate for fetal cranial shape) was not significantly different between those with and those without shoulder dystocia. The combination of estimated fetal weight, maternal diabetes, gender and AD - BPD provided a reasonable estimate of the individual risk. CONCLUSION: Sonographic fetal anthropometric measures appear not to be a useful tool to screen for the risk of shoulder dystocia due to a low PPV. However, AD - BPD appears to be a relevant risk factor. While risk stratification including different known risk factors may aid in counseling, shoulder dystocia cannot effectively be predicted.

Multiple embryonic sources converge to form the pectoral girdle skeleton in zebrafish.

The morphological transformation of the pectoral/shoulder girdle is fundamental to the water-to-land transition in vertebrate evolution. Although previous studies have resolved the embryonic origins of tetrapod shoulder girdles, those of fish pectoral girdles remain uncharacterized, creating a gap in the understanding of girdle transformation mechanisms from fish to tetrapods. Here, we identify the embryonic origins of the zebrafish pectoral girdle, including the cleithrum as an ancestral girdle element lost in extant tetrapods. Our combinatorial approach of photoconversion and genetic lineage tracing demonstrates that cleithrum development combines four adjoining embryonic populations. A comparison of these pectoral girdle progenitors with extinct and extant vertebrates highlights that cleithrum loss, indispensable for neck evolution, is associated with the disappearance of its unique developmental environment at the head/trunk interface. Overall, our study establishes an embryological framework for pectoral/shoulder girdle formation and provides evolutionary trajectories from their origin in water to diversification on land.

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

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.

Origin of the unique morphology of the shoulder girdle in turtles.

The shoulder girdle of turtles has a triradiate morphology. Although its dorsal process represents the scapular blade, the skeletal identities of the two ventral processes remain uncertain. To elucidate the question, developmental patterns of the girdles were compared between Chinese soft-shelled turtles, chickens, and mice. Despite the morphological diversity of adults, the initial primordia of the shoulder girdles showed similar morphological patterns. The ventral two processes developed from the anlagen comparable to those of the acromion and the coracoid in other amniotes. The developmental pattern of the acromion is very similar among embryos, whereas that of the coracoid in mammals differs from that in non-mammals, implying that coracoids are not homologous between non-mammals and mammals. Therefore, amniotes have retained the ancestral pattern of the girdle anlage, and the shoulder girdle of turtles has been achieved through a transformation of the pattern in the late ontogenic period.

Sprengel's deformity and spinal dysraphism: connecting the shoulder and the spine.

BACKGROUND AND PURPOSE: Sprengel's deformity, a rare congenital malformation of the scapula, may be observed in combination with spinal dysraphism. The co-occurrence of these malformations suggests an unknown shared etiology. Therefore, we reviewed the medical records of eight children presenting with both malformations and performed a review of the literature. PATIENTS AND METHODS: Databases from four university medical centers were searched for children presenting between 1992 and 2012 with spinal dysraphism and a Sprengel's deformity. CONCLUSION: The combination of spinal dysraphism and Sprengel's deformity is rare, and is associated with segmentation defects of the spine and ribs. Although the etiology of both spinal dysraphism and Sprengel's deformity remains unclear, all deformities of the spine, ribs, and shoulder might result from a common genetic defect affecting somitogenesis.

Neural crest origins of the neck and shoulder.

The neck and shoulder region of vertebrates has undergone a complex evolutionary history. To identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using Cre-recombinase-mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing the seemingly homogeneous skeleton of the neck and shoulders. Within this assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of both neural crest and mesodermal origin obey as they form muscle scaffolds. The neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox-gene-controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest-derived is specifically affected in human Klippel-Feil syndrome, Sprengel's deformity and Arnold-Chiari I/II malformation, providing insights into their likely aetiology. We identify genes involved in the cellular modularity of the neck and shoulder skeleton and propose a new method for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors, which seems to survive as the scapular spine in living mammals.

Shoulder girdle formation and positioning during embryonic and early fetal human development.

Positional information on the shoulder girdle (the clavicle and scapula) is important for a better understanding of the function of the upper limb in the locomotive system as well as its associated disease pathogenesis. However, such data are limited except for information on the axial position of the scapula. Here, we describe a three-dimensional reconstruction of the shoulder girdle including the clavicle and scapula, and its relationship to different landmarks in the body. Thirty-six human fetal specimens (crown-rump length range: 7.6-225 mm) from the Kyoto Collection were used for this study. The morphogenesis and three-dimensional position of the shoulder girdle were analyzed with phase-contrast X-ray computed tomography and magnetic resonance imaging. We first detected the scapula body along with the coracoid and humeral head at Carnegie stage 18; however, the connection between the body and coracoid was not confirmed at this stage. During development, all landmarks on the shoulder girdle remained at the same axial position except for the inferior angle, which implies that the scapula enlarged in the caudal direction and reached the adult axial position in the fetal period. The scapula body was rotated internally and in the upward direction at the initiation of morphogenesis, but in the fetal period the scapula body was different than that in the adult position. The shoulder girdle was located at the ventral side of the vertebrae at the time of initial morphogenesis, but changed its position to the lateral side of the vertebrae in the late embryonic and fetal periods. Such a unique position of the shoulder girdle may contribute to the stage-specific posture of the upper limb. Adequate internal and upward rotation of the scapula could help in reducing the shoulder width, thereby facilitating childbirth. The data presented in this study can be used as normal morphometric references for shoulder girdle evaluations in the embryonic and fetal periods.

Chondrogenesis and ossification of the lissamphibian pectoral girdle.

Knowledge of amphibian shoulder development is requisite for further understanding of gnathostome pectoral girdle evolution. Fish and amniotes share few pectoral girdle elements, but modern amphibians exhibit a unique combination of traits that bridge the morphological gap between these two groups. I analyzed patterns of chondrogenesis, ossification, and bone histology of the pectoral girdles of two anuran species (Xenopus laevis and Bombina orientalis) and two urodele species (Ambystoma mexicanum and Desmognathus aeneus) to provide new insight into the evolution of the tetrapod pectoral girdle. Comparisons reveal the following: 1) variation in the pattern of chondrogenesis among the anuran species analyzed correlates to variation in adult pectoral girdle morphology; 2) morphologically similar pectoral skeletons do not necessarily have similar patterns of bone histology; and 3) the urodele and anuran pectoral girdles included herein share a common morphology despite differences in patterns of chondrogenesis.

Development of the long head of the biceps brachial tendon: A possible explanation of the anatomical variations.

The anatomical variations of the proximal portion of the long head of the biceps brachii tendon (LHBT) are rarely observed in clinical practice. However, an increase in the rate of shoulder arthroscopic surgery has led to an increase in the observation of anatomical variations of this region. The aim of this work was to analyze the development of the LHBT in 23 human embryos ranging from the 6th to 8th weeks of development. The LHBT develops from the glenohumeral interzonal mesenchyme in the 6th week. By week 7, the myotendinous junction of the LHBT develops. The anlage of the LHBT is separated from that of the glenohumeral capsule during week 8. Our results suggest that the most important period for the LHBT development occurs between the 6th and 8th weeks of embryonic development. Alterations during this critical period may cause anatomical variations of the LHBT. An additional case report from our own experience is provided as Supplementary material.

Shoulder dystocia: prevention and management.

Knowledge of the maneuvers used for the alleviation of shoulder dystocia is relevant not only for obstetric residents and attending house staff but also for family practitioners, nurses, and nurse midwives. The performance of shoulder dystocia "drills" can be helpful not only to coordinate a teamwork approach to this obstetric emergency but also to provide an opportunity to practice the maneuvers. Shoulder dystocia continues to represent an immense area of clinical interest because it typically occurs without prediction. All patients in labor should be considered at risk for the development of shoulder dystocia.

Constraints on the morphological evolution of marsupial shoulder girdles.

Throughout their evolutionary histories, marsupial mammals have been taxonomically and morphologically less diverse than their sister taxa the placentals. Because of this, it has been proposed that the evolution of marsupials has been constrained by the functional requirements of their mode of reproduction. Marsupials give birth after short gestation times to immature neonates that immediately crawl, under the power of their precociously developed shoulder girdles, to the teat where they attach and complete their early development. Using a novel approach incorporating adult and embryological morphological data, this study is the first to both: (1) statistically support adult patterns of morphological divergence consistent with the constraint hypothesis, and (2) identify ontogenetic patterns of morphological change that demonstrate that the constraint was responsible, at least in part, for their formation. As predicted by the marsupial constraint, the shoulder girdles of adult marsupials are less diverse than those of adult placentals, and adult marsupial scapulae are less morphologically diverse than adult marsupial pelves. Furthermore, marsupials that complete an extensive crawl to the teat are restricted to a common pattern of ontogenetic scapular shape change, strongly supporting the hypothesis that the morphological development of the marsupial scapula has been limited evolutionarily by its obligate role in the crawl to the teat. Because this study establishes that ontogenetic and evolutionary morphological change is correlated within mammalian scapulae, it is probable that the marsupial constraint also restricted the morphological divergence of the scapula over evolutionary time by limiting ontogenetic change in the scapula. These findings, coupled with the importance of the shoulder girdle in mammalian locomotor specialization, support the conclusion that the low morphological diversity of marsupial forms over evolutionary time could be directly due to the constraint on marsupial morphological evolution caused by the functional requirements of the crawl to the teat.

Ontogenesis of the scapula in marsupial mammals, with special emphasis on perinatal stages of didelphids and remarks on the origin of the therian scapula.

The development of the scapula was studied in embryonic and postnatal specimens of Monodelphis domestica and perinatal specimens of Philander opossum, Caluromys philander, and Sminthopsis virginiae using histological sections and 3D reconstructions. Additionally, macerated skeletons of postnatal M. domestica were examined. This study focused on the detachment of the scapulocoracoid from the sternum and on the acquisition of a supraspinous fossa, a supraspinatus muscle, and a scapular spine, all these events associated with the origin of the therian shoulder girdle. In none of the specimens is there a continuity of the cartilaginous scapulocoracoid with the sternum, even though the structures are in close proximity, especially in S. virginiae. At birth, the first rib laterally presents a pronounced boss that probably contacts the humerus during certain movements. Only the acromial portion of the scapular spine, which originates from the anterior margin of the scapular blade, is preformed in cartilage. The other portion is formed by appositional bone ("Zuwachsknochen"), which expands from the perichondral ossification of the scapula into an intermuscular aponeurosis between the supra- and infraspinous muscles. This intermuscular aponeurosis inserts more or less in the middle of the lateral surface of the developing scapula. Thus, the floor of the supraspinous fossa is present from the beginning of scapular development, simultaneously with the infraspinous fossa. The homology of the therian spine with the anterior border of the sauropsid and monotreme scapula is questioned. We consider the dorsal portion (as opposed to the ventral or acromial portion) of the scapular spine a neomorphic structure of therian mammals.

Neural crest does not contribute to the neck and shoulder in the axolotl (Ambystoma mexicanum).

BACKGROUND: A major step during the evolution of tetrapods was their transition from water to land. This process involved the reduction or complete loss of the dermal bones that made up connections to the skull and a concomitant enlargement of the endochondral shoulder girdle. In the mouse the latter is derived from three separate embryonic sources: lateral plate mesoderm, somites, and neural crest. The neural crest was suggested to sustain the muscle attachments. How this complex composition of the endochondral shoulder girdle arose during evolution and whether it is shared by all tetrapods is unknown. Salamanders that lack dermal bone within their shoulder girdle were of special interest for a possible contribution of the neural crest to the endochondral elements and muscle attachment sites, and we therefore studied them in this context. RESULTS: We grafted neural crest from GFP+ fluorescent transgenic axolotl (Ambystoma mexicanum) donor embryos into white (d/d) axolotl hosts and followed the presence of neural crest cells within the cartilage of the shoulder girdle and the connective tissue of muscle attachment sites of the neck-shoulder region. Strikingly, neural crest cells did not contribute to any part of the endochondral shoulder girdle or to the connective tissue at muscle attachment sites in axolotl. CONCLUSIONS: Our results in axolotl suggest that neural crest does not serve a general function in vertebrate shoulder muscle attachment sites as predicted by the "muscle scaffold theory," and that it is not necessary to maintain connectivity of the endochondral shoulder girdle to the skull. Our data support the possibility that the contribution of the neural crest to the endochondral shoulder girdle, which is observed in the mouse, arose de novo in mammals as a developmental basis for their skeletal synapomorphies. This further supports the hypothesis of an increased neural crest diversification during vertebrate evolution.

Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes.

The diverse cellular contributions to the skeletal elements of the vertebrate shoulder and pelvic girdles during embryonic development complicate the study of their patterning. Research in avian embryos has recently clarified part of the embryological basis of shoulder formation. Although dermomyotomal cells provide the progenitors of the scapular blade, local signals appear to have an essential guiding role in this process. These signals differ from those that are known to pattern the more distal appendicular skeleton. We have studied the impact of Tbx15, Gli3, Alx4 and related genes on formation of the skeletal elements of the mouse shoulder and pelvic girdles. We observed severe reduction of the scapula in double and triple mutants of these genes. Analyses of a range of complex genotypes revealed aspects of their genetic relationship, as well as functions that had been previously masked due to functional redundancy. Tbx15 and Gli3 appear to have synergistic functions in formation of the scapular blade. Scapular truncation in triple mutants of Tbx15, Alx4 and Cart1 indicates essential functions for Alx4 and Cart1 in the anterior part of the scapula, as opposed to Gli3 function being linked to the posterior part. Especially in Alx4/Cart1 mutants, the expression of markers such as Pax1, Pax3 and Scleraxis is altered prior to stages when anatomical aberrations are visible in the shoulder region. This suggests a disorganization of the proximal limb bud and adjacent flank mesoderm, and is likely to reflect the disruption of a mechanism providing positional cues to guide progenitor cells to their destination in the pectoral girdle.