4D formation of human embryonic forelimb musculature.

The size, shape and insertion sites of muscles enable them to carry out their precise functions in moving and supporting the skeleton. Although forelimb anatomy is well described, much less is known about the embryonic events that ensure individual muscles reach their mature form. A description of human forelimb muscle development is needed to understand the events that control normal muscle formation and to identify what events are disrupted in congenital abnormalities in which muscles fail to form normally. We provide a new, 4D anatomical characterisation of the developing human upper limb muscles between Carnegie stages 18 and 22 using optical projection tomography. We show that muscles develop in a progressive wave, from proximal to distal and from superficial to deep. We show that some muscle bundles undergo splitting events to form individual muscles, whereas others translocate to reach their correct position within the forelimb. Finally, we show that palmaris longus fails to form from early in development. Our study reveals the timings of, and suggests mechanisms for, crucial events that enable nascent muscle bundles to reach their mature form and position within the human forelimb.

Upper limb arterial pattern: clinical correlation and embryological perspective / Padrão arterial dos membros superiores: correlação clínica com perspectiva embriológica

Abstract Background Variations in the upper limb arterial pattern are commonplace and necessitate complete familiarity for successful surgical and interventional procedures. Variance in the vascular tree may involve any part of the axis artery of the upper limb, including the axillary artery and brachial artery or its branches, in the form of radial and ulnar arteries, which eventually supply the hand via anastomosing arches. Objectives To study the peculiarities of the arterial pattern of the upper limb and to correlate them with embryological development. Methods The entire arterial branching of forty-two upper limbs of formalin fixed adult human cadavers was examined during routine dissection for educational purposes, conducted over a 3-year period in the Department of Anatomy, Lady Hardinge Medical College, New Delhi. Results The study found: 1) One case in which a common trunk arose from the third part of the axillary artery, which immediately splayed into four branches (2.4%); 2) High division of the brachial artery into ulnar and radial arteries, in 3 cases (7.1%); 3) Pentafurcation of the brachial artery into ulnar, interosseus, radial, and radial recurrent arteries and a muscular twig to the brachioradialis in 1/42 cases (2.4%); 4) Incomplete Superficial Palmar arch in 3/42 cases (7.1%); and 5) Presence of a median artery in 2/42 case(4.8%) Conclusions This study observed and described the varied arterial patterns of the upper limb and identified the various anomalous patterns, supplementing the surgeon's armamentarium in various surgical procedures, thereby helping to prevent complications or failures of reconstructive surgeries, bypass angiography, and many similar procedures.

Resumo Contexto As variações no padrão arterial dos membros superiores são comuns e, assim, necessitam de total familiaridade para que os procedimentos cirúrgicos e de intervenção sejam bem-sucedidos. A variância na árvore vascular pode envolver qualquer parte da artéria axial dos membros superiores, incluindo a artéria axilar, a artéria braquial ou os seus ramos, na forma das artérias radial e ulnar, as quais, em algum momento, suprem as mãos através dos arcos anastomosados. Objetivos Avaliar as peculiaridades do padrão arterial dos membros superiores e correlacioná-las ao desenvolvimento embriológico. Métodos Foram examinados os ramos arteriais completos de 42 membros superiores de cadáveres adultos conservados em formalina, os quais eram rotineiramente dissecados para fins educacionais durante 3 anos no Departamento de Anatomia Lady Hardinge Medical College, Nova Delhi. Resultados O estudo apresentou cinco desfechos. 1. Foi constatado um caso em que um tronco comum surgiu da terceira parte da artéria axilar que imediatamente se disseminou em quatro ramos (2,4%). 2. Houve divisão maior da artéria braquial em artérias ulnar e radial em três casos (7,1%). 3. Em um caso, ocorreu pentafurcação da artéria braquial em ulnar, interóssea, radial, radial recorrente e de um galho muscular em braquiorradial (2,4%). 4. Foi constatado arco palmar superficial incompleto em três dos 42 casos (7,1%). 5. Foi observada a presença da artéria mediana em 2 dos 42 casos (4,8%). Conclusões Este estudo compreende o padrão arterial do membro superior e identifica os diversos padrões anômalos para agregar ao arsenal terapêutico de cirurgiões para diversos procedimentos cirúrgicos, com o objetivo de combater quaisquer complicações ou falhas de cirurgias reconstrutivas, de angiografias de cirurgias de revascularização e muitas outras.

An unusual case of primate arterial pattern in a human upper limb / Un caso inusual de patrón arterial de primates en un miembro superior humano

During routine undergraduate dissections of the upper limb, variations on the usual arterial and muscular patterns were observed in a 68 year-old male cadaver. The arterial and muscular pattern found in our specimen is similar to that of some primates in the following terms. 1) Brachial artery duplicity, on the right side, with a superficial brachio-ulnoradial artery. 2) In the right upper limb, the biceps brachii muscle continued with the superficial muscles of the forearm. 3) The brachial artery on the left side, cross over in front of the median nerve, as the only artery of the arm with a network axillary pattern. 4) On both sides, the ulnar artery was superficial and originated at the elbow from superficial brachial arteries. 5) The right anterior interosseous artery intervened in the vascularization of the hand. These results suggest that this may be a case of early detention of human embryonic development and/or the persistence of phylogenetic older patterns. In the literature, we have found no reference to the presence of all these variations in the same individual. The objective of our study was to analyze these variations from an embryological and phylogenetic perspective.

Durante las disecciones de pregrado de rutina del miembro superior, se observaron variaciones en los patrones arteriales y musculares habituales en un cadáver macho de 68 años. El patrón arterial y muscular que se encuentra en nuestro espécimen es similar al de algunos primates en los siguientes términos. 1) Duplicidad de la arteria braquial, en el lado derecho, con una arteria braquioulnoradial superficial. 2) En el miembro superior derecho, el músculo bíceps braquial continuó con los músculos superficiales del antebrazo. 3) La arteria braquial en el lado izquierdo, se cruza frente al nervio mediano, como la única arteria del brazo con un patrón axilar en red. 4) En ambos lados, la arteria ulnar era superficial y se originó en el codo de las arterias braquiales superficiales. 5) La arteria interósea anterior derecha intervino en la vascularización de la mano. Estos resultados sugieren que este puede ser un caso de detención temprana del desarrollo embrionario humano y/o la persistencia de patrones filogenéticos más antiguos. En la literatura, no hemos encontrado ninguna referencia a la presencia de todas estas variaciones en el mismo individuo. El objetivo de nuestro estudio fue analizar estas variaciones desde una perspectiva embriológica y filogenética.

Developmental biology of the upper limb.

This article aims to provide hand surgeons with current knowledge on the developmental biology of the upper limb. It will review positioning, limb bud emergence and formation of the apical ectodermal ridge. The development of the limb bud is analyzed in its three axes: proximal-distal, anteroposterior and dorsoventral. The signaling center and primary morphogens that initiate and stimulate the development of each axis will be described. For the proximal-distal axis, the apical ectodermal ridge stimulates the production of FGFs in the underlying distal mesoderm. The anteroposterior (or radio-ulnar) differentiation is a function of the zone of polarizing activity via the small Sonic hedgehog protein, which diffuses in a decreasing concentration gradient from the ulnar to the radial side of the bud. This gradient is essential to digit identity and numbers. For the dorsoventral differentiation, the signaling center is the dorsal ectoderm, which secretes WNT7A. Limb segmentation is described in three parts (arm, forearm and hand) along with the formation of the digital rays until finger separation. An example of congenital anomalies is provided for each step. To keep the length of this lecture within reason, the embryogenesis of nerves, blood vessels, muscles and tendons will not be discussed. On the other hand, the singularity of the thumb relative to the other fingers will be described. With a better understanding of developmental biology, surgeons should have better insight into congenital anomalies of the upper limb. This approach is the basis for the new OMT classification used by the IFFSH.

MR microscopy of the human fetal upper extremity - a proof-of-principle study.

BACKGROUND: Current knowledge of the human fetal and embryonic development relies on early descriptive studies of humans and from experimental studies of laboratory animals and embryos. Taking the upper extremity as an example, this study explores the potential of magnetic resonance microscopy (MRM) for the assessment of the development of the fetal upper extremity and discusses its correlation with histological findings. METHODS: Ex vivo MRM at 7.1 T (Clin Scan, Bruker Biospin, Germany) was performed in 10 human specimens at 8 to 12 weeks of gestational age (GA). In-plane resolution was 20 µm with a slice thickness of 70 µm. MRM was followed by histological work-up of the specimens. MRM images were then correlated with conventional histology with a focus on the presence of chondrification and ossification. RESULTS: Ossification of the upper human extremity is detectable at 8 weeks GA in the humerus and the long bones of the forearm. There is excellent correlation for location and size of ossification between MRM and conventional histology. MRM imaging is in accordance with historical studies. CONCLUSION: Ex vivo MRM for the non-invasive assessment of the embryonic and fetal development of the upper human extremity is feasible. It may provide an accurate complementary tool for the evaluation of embryological development.

Developmental stages of the climbing gecko Tarentola annularis with special reference to the claws, pad lamellae, and subdigital setae.

Studying the in ovo mode of development of squamates has the advantage of allowing easy access to embryos without surgically compromising gravid females. Despite the non-ophidian squamates being a very diverse lineage of reptiles, embryonic tables for individuals of this group are very few. Here, I present the first in ovo embryonic table for a basal multi-scansored, pad-bearing gecko, Tarentola annularis. In this gecko, only the III and IV digits bear claws. Eleven embryonic stages are described based on chronological development of morphological characteristics. In contrast to other previously studied geckos, this species exhibits a longer incubation period. Comparison with other squamates, embryonic development of T. annularis is an indicative of a conserved developmental strategy. Interestingly, the clawless digits of this gecko do exhibit claws during the first half of embryonic development. Thus, regression of claws in these digits could be an advantage of studying this particular taxon, as it raises the question, to be answered in future study, of which mechanisms could be responsible for such claw regression. Before hatching, the outer periderm layer sloughs revealing the functional setae. The present study provides not only a model for pentadactyl limbs and digit development, but also an example of a unique developmental phenomenon, as represented by claw regression.

The anatomy and ontogeny of the head, neck, pectoral, and upper limb muscles of Lemur catta and Propithecus coquereli (primates): discussion on the parallelism between ontogeny and phylogeny and implications for evolutionary and developmental biology.

Most anatomical studies of primates focus on skeletal tissues, but muscular anatomy can provide valuable information about phylogeny, functional specializations, and evolution. Herein, we present the first detailed description of the head, neck, pectoral, and upper limb muscles of the fetal lemuriforms Lemur catta (Lemuridae) and Propithecus coquereli (Indriidae). These two species belong to the suborder Strepsirrhini, which is often presumed to possess some plesiomorphic anatomical features within primates. We compare the muscular anatomy of the fetuses with that of infants and adults and discuss the evolutionary and developmental implications. The fetal anatomy reflects a phylogenetically more plesiomorphic condition in nine of the muscles we studied and a more derived condition in only two, supporting a parallel between ontogeny and phylogeny. The derived exceptions concern muscles with additional insertions in the fetus which are lost in adults of the same species, that is, flexor carpi radialis inserts on metacarpal III and levator claviculae inserts on the clavicle. Interestingly, these two muscles are involved in movements of the pectoral girdle and upper limb, which are mainly important for activities in later stages of life, such as locomotion and prey capture, rather than activities in fetal life. Accordingly, our findings suggest that some exceptions to the "ontogeny parallels phylogeny" rule are probably driven more by ontogenetic constraints than by adaptive plasticity.

When right differs from left: human limb directional asymmetry emerges during very early development.

The often observed directional asymmetry (DA) in human limb bones may have a genetic/developmental basis and/or could emerge from different mechanical loadings across sides due to handedness. Because behavioural lateralization in itself has a genetic basis, it has been suggested that DA in limbs could develop prenatally as a pre-adaptation to adult life. However, the presence of consistent differences in the size of left and right limb bones in early development is understudied. We study asymmetry in limb bones during early development (10-20 weeks of gestation) in a sample of 178 aborted foetuses. Statistically significant DA was found in several upper and lower limb bones, where the right-hand side was consistently larger than the left. We argue that this pattern is probably the consequence of developmental processes related to internal asymmetric positioning of organs.

Update on embryology of the upper limb.

Current concepts in the steps of upper limb development and the way the limb is patterned along its 3 spatial axes are reviewed. Finally, the embryogenesis of various congenital hand anomalies is delineated with an emphasis on the pathogenetic basis for each anomaly.

Classification of dorsal and ventral dimelia in humans.

Dorsal dimelia (appearance of dorsal structures on the palmar aspect of the hand) and ventral dimelia (appearance of palmar structures on the dorsal aspect of the hand) are rare congenital hand malformations that occur due to errors of the dorso-ventral axis of development of the limb. The current literature includes numerous cases and there is now sufficient basic science/genetics research on the topic so that a classification of dorsal/ventral dimelia could be proposed. Dorsal dimelia is subclassified into two types: distal (dorsalization of the digits ± distal palm) and proximal (dorsalization of the proximal palm only) types. Ventral dimelia is classified into three types (mild, moderate, and severe) according to the degree of ventralization. The classification is supported by the genetic basis of each subtype.

Caracterización de las anomalías congénitas del Miembro superior en una institución prestadora de servicios de salud de Ibagué, Tolima, Colombia / Characterization of congenital anomalies of the upper member in an institution health care provider of Ibague, Tolima, Colombia

El objetivo de este estudio fue caracterizar las historias clínicas de los pacientes con diagnóstico de Anomalías Congénitas del Miembro Superior (ACMS), en un centro de referencia en la atención de malformaciones congénitas en la ciudad de Ibagué, Tolima, Colombia. Estudio descriptivo, retrospectivo. Se incluyeron todas las historias clínicas de los pacientes con diagnóstico de anomalías congénitas del miembro superior. Las ACMS se agruparon según la clasificación Swanson, modificada por la International Federation ofSocieties for Surgery of the Hand (Swanson/IFSSH). Se calcularon medias y porcentajes de las ACMS, género y distribución geográfica,frecuencia de malformaciones asociadas, lateralidad, intervención quirúrgica, número de intervenciones y co-morbilidades. Se evaluó un total de 194 casos (55,7% hombres y 44,3% mujeres). La edad promedio de consulta fue de 7,82±6,69 años. El 40,7%procedía de la ciudad de Ibagué, y el porcentaje restante de municipios aledaños y otros departamentos. Las más frecuentes fueron polidactilia radial(16,02%), deficiencia del rayo central (14,72%), sindáctila cutánea (11,26%). Se estimó una tasa cruda de incidencia para el departamento del Tolima en el año 2001 de 7,8/10.000 nacidos vivos, en el año 2002 de 8,6/10.000 nacidos vivos y en el año 2004 de 6,5/10.000 nacidos vivos. Conclusiones: Dadas las implicaciones en la funcionalidad, desarrollo cognitivo y productividad laboral de los pacientes con ACMS, se recomienda implementar un sistema de vigilancia epidemiológica que permita discriminar las anomalíascongénitas, según su ubicación anatómica, de tal forma que facilite su análisis y permita definir conductas adecuadas.

This study characterized the clinical records of patients diagnosed with Congenital Upper Extremity Anomalies (CUEA) in a referencecenter in the care of congenital malformations in the city of Ibagué, Tolima, Colombia. Methods: A descriptive, retrospective study wasdone. We included all clinical records of patients diagnosed with CUEA. The CUEA were classified according Swanson modified by the International Federation of Societies for Surgery of the Hand system (Swanson/IFSSH). Means and percentages were calculated from theCUEA, gender and site distribution, frequency of associated deformities, laterality, surgical intervention, number of interventions and comorbidities.Results: A total of 197 cases (55.7% male and 44.3% female). The average age of consultation was 7.82 years ± 6.69; 40.7% came from Ibagué and the rest from the neighboring municipalities and other departments. The most common CUEA was radial polydactyly (16.02%), followed by central ray deficiency (14.72%), and cutaneous syndactyly (11.26%). We estimated crude incidence rate for the department of Tolima in 2001 of 7.8 per 10,000 live births, in 2002 of 8.6 per 10,000 live births and in 2004 6.5 per 10,000live births. Conclusions: Given the implications in the functionality, cognitive development and labor productivity of patients withCUEA, it is recommended to implement a surveillance system that allows discrimination of the congenital deformities, according to theiranatomical location, so as to facilitate analysis and to define appropriate behaviors.

Neogenin regulates Sonic Hedgehog pathway activity during digit patterning.

BACKGROUND: Digit patterning integrates signaling by the Sonic Hedgehog (SHH), fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) pathways. GLI3, a component of the SHH pathway, is a major regulator of digit number and identity. Neogenin (encoded by Neo1) is a cell surface protein that serves to transduce signals from several ligands, including BMPs, in various developmental contexts. Although neogenin is implicated in BMP signaling, it has not been linked to SHH signaling and its role in digit patterning is unknown. RESULTS: We report that Neo1 mutant mice have preaxial polydactyly with low penetrance. Expression of SHH target genes, but not BMP target genes, is altered in Neo1 mutant limb buds. Analysis of mice carrying mutations in both Neo1 and Gli3 reveals that, although neogenin plays a role in constraint of digit numbers, suppressing polydactyly, it is also required for the severe polydactyly caused by loss of GLI3. Furthermore, embryo fibroblasts from Neo1 mutant mice are sensitized to SHH pathway activation in vitro. CONCLUSIONS: Our findings indicate that neogenin regulates SHH signaling in the limb bud to achieve proper digit patterning.

A review of supernumerary and absent limbs and digits of the upper limb.

For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12-23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb.

Molecular control of cell differentiation and programmed cell death during digit development.

During the hand plate development, the processes of cell differentiation and control of cell death are relevant to ensure a correct shape of the limb. The progenitor cell pool that later will differentiate into cartilage to form the digits arises from undifferentiated mesenchymal cells beneath the apical ectodermal ridge (AER). Once these cells abandon the area of influence of signals from AER and ectoderm, some cells are committed to chondrocyte lineage forming the digital rays. However, if the cells are not committed to chondrocyte lineage, they will form the prospective interdigits that in species with free digits will subsequently die. In this work, we provide the overview of the molecular interactions between different signaling pathways responsible for the formation of digit and interdigit regions. In addition, we briefly describe some experiments concerning the most important signals responsible for promoting cell death. Finally, on the basis that the interdigital tissue has chondrogenic potential, we discuss the hypothesis that apoptotic-promoting signals might also act as antichondrogenic factors and chondrogenic factors might operate as anti-apoptotic factors.

Defective cranial skeletal development, larval lethality and haploinsufficiency in Myod mutant zebrafish.

Myogenic regulatory factors of the myod family (MRFs) are transcription factors essential for mammalian skeletal myogenesis. Here we show that a mutation in the zebrafish myod gene delays and reduces early somitic and pectoral fin myogenesis, reduces miR-206 expression, and leads to a persistent reduction in somite size until at least the independent feeding stage. A mutation in myog, encoding a second MRF, has little obvious phenotype at early stages, but exacerbates the loss of somitic muscle caused by lack of Myod. Mutation of both myod and myf5 ablates all skeletal muscle. Haploinsufficiency of myod leads to reduced embryonic somite muscle bulk. Lack of Myod causes a severe reduction in cranial musculature, ablating most muscles including the protractor pectoralis, a putative cucullaris homologue. This phenotype is accompanied by a severe dysmorphology of the cartilaginous skeleton and failure of maturation of several cranial bones, including the opercle. As myod expression is restricted to myogenic cells, the data show that myogenesis is essential for proper skeletogenesis in the head.