Initial stages of development of the submandibular gland (human embryos at 5.5–8 weeks of development)

The aim of this study was to determine the main stages of submandibular salivary gland development during the embryonic period in humans. In addition, we studied submandibular salivary gland development in rats on embryonic days 14–16 and expression in the submandibular salivary gland region with the monoclonal antibody HNK‐1. Serial sections from 25 human embryos with a greatest length ranging from 10 to 31 mm (Carnegie stages 16–23; weeks 5.5–8 of development) and Wistar rats of embryonic days (E) 14–16 were analysed with light microscopy. Five stages of submandibular salivary gland development were identified. The prospective stage (1), between weeks 5.5 and early week 6, is characterized by a thickening of the epithelium of the medial paralingual groove in the floor of the mouth corresponding to the primordium of the submandibular salivary gland parenchyma. At this stage, the primordium of the parasympathetic ganglion lies below the lingual nerve. The primordium of the submandibular salivary gland parenchyma is observed in rats on E14 in the medial paralingual groove with mesenchymal cells, underlying the lingual nerve. These cells are HNK‐1‐positive, corresponding to the primordium of the parasympathetic ganglion. The bud stage (2), at the end of week 6 in humans and on E15 in rats, is characterized by the proliferation and invagination of the epithelial condensation, surrounded by an important condensation of the mesenchyme. The pseudoglandular stage (3) at week 6.5 is characterized by the beginning of the formation of lobes in the condensed mesenchyme. The canalicular stage (4), between week 7 and 7.5, is characterized by the appearance of a lumen in the proximal part of the submandibular duct. The innervation stage (5) occurs during week 8, with the innervation of the submandibular and interlobular ducts. Nervous branches arriving from the parasympathetic ganglion innervate the glandular parenchyma. Numerous blood vessels are observed nearby. Our results suggest that submandibular salivary gland development requires interactions among epithelium, mesenchyme, parasympathetic ganglion and blood vessels.     

A new ontology (structured hierarchy) of human developmental anatomy for the first 7 weeks (Carnegie stages 1–20)

This paper describes a new ontology of human developmental anatomy covering the first 49 days [Carnegie stages (CS)1–20], primarily structured around the parts of organ systems and their development. The ontology includes more than 2000 anatomical entities (AEs) that range from the whole embryo, through organ systems and organ parts down to simple or leaf tissues (groups of cells with the same morphological phenotype), as well as features such as cavities. Each AE has assigned to it a set of facts of the form <AE><relationship><parent>, with the relationships including starts_at and ends_at (CSs), part_of (there can be several parents) and is_a (this gives the type of tissue, from an organ system down to one of ~ 80 simple tissues predominantly composed of a single cell kind, which is also specified). Leaf tissues also have a develops_from link to its parent tissue. The ontology includes ~14 000 such facts, which are mainly from the literature and an earlier ontology of human developmental anatomy (EHDAA, now withdrawn). The relationships enable these facts to be integrated into a single, complex hierarchy (or mathematical graph) that was made and can be viewed in the OBO‐Edit browser ( oboedit.org ). Each AE has an EHDAA2 ID that may be useful in an informatics context, while the ontology as a whole can be used for organizing databases of human development. It is also a knowledge resource: a user can trace the lineage of any tissue back to the egg, study the changes in cell phenotype that occur as a tissue develops, and use the structure to add further (e.g. molecular) information. The ontology may be downloaded from www.obofoundry.org . Queries and corrections should be sent to j.bard@ed.ac.uk .     

The deep fascia and retinacula of the equine forelimb – structure and innervation

Recent advances in human fascia research have shed new light on the role of the fascial network in movement perception and coordination, transmission of muscle force, and integrative function in body biomechanics. Evolutionary adaptations of equine musculoskeletal apparatus that assure effective terrestrial locomotion are employed in equestrianism, resulting in the wide variety of movements in performing horses, from sophisticated dressage to jumping and high‐speed racing. The high importance of horse motion efficiency in the present‐day equine industry indicates the significance of scientific knowledge of the structure and physiology of equine fasciae. In this study, we investigated the structure and innervation of the deep fascia of the equine forelimb by means of anatomical dissection, histology and immunohistochemistry. Macroscopically, the deep fascia appears as a dense, glossy and whitish lamina of connective tissue continuous with its fibrous reinforcements represented by extensor and flexor retinacula. According to the results of our histological examination, the general structure of the equine forelimb fascia corresponds to the characteristics of the human deep fasciae of the limbs. Although we did find specific features in all sample types, the general composition of all examined fascial tissues follows roughly the same scheme. It is composed of dense, closely packed collagen fibers organized in layers of thick fibrous bundles with sparse elastic fibers. This compact tissue is covered from both internal and external sides by loosely woven laminae of areolar connective tissue where elastic fibers are mixed with collagen. Numerous blood vessels running within the loose connective tissue contribute to the formation of regular vascular network throughout the compact layer of the deep fascia and retinacula. We found nerve fibers of different calibers in all samples analyzed. The fibers are numerous in the areolar connective tissue and near the blood vessels but scarce in the compact layers of collagen. We did not observe any Ruffini, Pacini or Golgi‐Mazzoni corpuscles. In conclusion, the multilayered composition of compact bundles of collagen, sparse elastic fibers in the deep fascia and continuous transition into retinacula probably facilitate resistance to gravitational forces and volume changes during muscle contraction as well as transmission of muscle force during movement. However, further research focused on innervation is needed to clarify whether the deep fascia of the equine forelimb plays a role in proprioception and movement coordination.     

Suprahyoid neck fascial configuration,especially in the posterior compartment of the parapharyngeal space: A histological study using late‐stage human fetuses

The fascial configuration in the suprahyoid parapharyngeal space was evaluated using semiserial sagittal sections of 15 late‐stage human fetal heads. The prevertebral fascia covered the longus colli, longus capitis, and rectus capitis lateralis muscles, but was most evident along the longus colli muscle. The carotid sheath and its extension were located around the internal and external carotid arteries and the lower cranial nerves. The superior cervical ganglion was also inside the sheath. Even near full term, the fetal suprahyoid neck was short, with the jugular foramen and hypoglossal canal located at the posterolateral side of the oropharynx. Thus, the glossopharyngeal and accessory nerves ran across the upper part of the carotid sheath. Fasciae of the stylopharyngeus, styloglossus, and stylohyoideus muscles were attached to and joined the anterosuperior aspect of the carotid sheath. All these neurovascular and muscle sheaths are communicated with the visceral fascia covering the pharynx at multiple sites, and, together, they formed a mesentery‐like bundle. This communication bundle was made narrow by the anteriorly protruding longus capitis muscle. The mesentery‐like bundle was covered by the posterior marginal fascia of the prestyloid compartment of the parapharyngeal space. The external carotid artery ran on the lateral and posterior sides of the posterior marginal fascia. Consequently, the typical carotid sheath configuration was modified by muscle sheaths from the styloid process, communicated with the visceral fascia and, anteriorly, constituted the posterior margin of the prestyloid space. Clin. Anat. 2013. © 2012 Wiley Periodicals, Inc.     

Enhanced gamma (30–150 Hz) frequency in the human medial temporal lobe

We performed fast Fourier transformation power spectral analysis of the electrocorticogram in human medial temporal lobe during wakeful rest in six epileptic subjects. Compared with the electrocorticogram wave in the basal temporal lobe, which showed monotonic decline of spectral power across the frequency axis, the electrocorticogram wave in the parahippocampal gyrus was enhanced (or did not decline) in the gamma frequency range (30–150 Hz) in all subjects.

Although it has been suggested that electrical oscillations of the hippocampus have functional roles in higher brain functions, namely learning and memory, the knowledge of hippocampal oscillations is largely limited to animal studies. The present results demonstrate that fast frequency oscillation is also present in the human medial temporal lobe, which has been reported in animal hippocampi. They also demonstrate the importance of recording very fast field potentials in human electrocorticograms. This fast oscillation is likely to play important functional roles related to learning and memory, possibly to induce long-term potentiation in the human medial temporal lobe.     

Linkage analysis of left ventricular outflow tract malformations (aortic valve stenosis, coarctation of the aorta, and hypoplastic left heart syndrome)

The left ventricular outflow tract (LVOT) malformations aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS) are significant causes of infant mortality. These three malformations are thought to share developmental pathogenetic mechanisms. A strong genetic component has been demonstrated earlier, but the underlying genetic etiologies are unknown. Our objective was to identify genetic susceptibility loci for the broad phenotype of LVOT malformations. We genotyped 411 microsatellites spaced at an average of 10 cM in 43 families constituting 289 individuals, with an additional 5 cM spaced markers for fine mapping. A non-parametric linkage (NPL) analysis of the combined LVOT malformations gave three suggestive linkage peaks on chromosomes 16p12 (NPL score (NPLS)=2.52), 2p23 (NPLS=2.41), and 10q21 (NPLS=2.14). Individually, suggestive peaks for AVS families occurred on chromosomes 16p12 (NPLS=2.64), 7q36 (NPLS=2.31), and 2p25 (NPLS=2.14); and for CoA families on chromosome 1q24 (NPLS=2.61), 6p23 (NPLS=2.29), 7p14 (NPLS=2.27), 10q11 (NPLS=1.98), and 2p15 (NPLS=2.02). Significant NPLS in HLHS families were noted for chromosome 2p15 (NPLS=3.23), with additional suggestive peaks on 19q13 (NPLS=2.16) and 10q21 (NPLS=2.07). Overlapping linkage signals on 10q11 (AVS and CoA) and 16p12 (AVS, CoA, and HLHS) led to higher NPL scores when all malformations were analyzed together. In conclusion, we report suggestive evidence for linkage to chromosomes 2p23, 10q21, and 16p12 for the LVOT malformations of AVS, CoA, and HLHS individually and in a combined analysis, with a significant peak on 2p15 for HLHS. Overlapping linkage peaks provide evidence for a common genetic etiology.     

Early pregnancy factor is required at two important stages of embryonic development in the mouse

PROBLEM: The importance of early pregnancy factor (EPF) at the pre-implantation stage of development (days 1-3 post-coitum [p.c.]) has been previously established in this laboratory. However, the role of EPF at the implantation stage (days 4.5-5 p.c.) has not been determined. This present study therefore investigates the role of EPF at this important developmental stage, both in vivo and in vitro. METHOD OF STUDY: Mated mice were passively immunized with anti-EPF antibodies at the peri-implantation stage (days 3.5-4 p.c.) and embryo implantation recorded. Parallel studies were conducted in vitro, where the effect of anti-EPF antibodies on trophoblast outgrowth of blastocysts was determined. RESULTS: Administration of anti-EPF antibodies in vivo at the peri-implantation stage of development resulted in failure of embryos to implant. Similarly, trophoblastic outgrowth of blastocysts was adversely affected in the presence of anti-EPF antibodies. CONCLUSIONS: These results, together with previous findings that anti-EPF antibodies retard embryonic development when administered at the early pre-implantation stage, clearly demonstrate that EPF is required by the embryo at two important developmental stages- the one-two-cell stage and the peri-implantation stage.     

Development of the human tensor veli palatini: specimens measuring 13.6-137 mm greatest length; weeks 6-16 of development

The present study seeks to determine the main events that occur in the development of the tensor veli palatini (TVP). A light microscope was used on serial sections of 60 human specimens from weeks 6 to 16 of development. The TVP becomes visible in an embryo of 14.5 mm greatest length (GL; week 6) from a common blastema with the medial pterygoid muscle. In embryos of Carnegie stage 20 (week 7), the TVP is differentiated and relates to the anlage of the pterygoid hamulus. At week 8 of development, when the palatal shelves become horizontal, the presence of the anlage of the palatine aponeurosisis distinguished and is reached by the TPV. In an embryo of 30 mm GL, the chondrification nucleus of the pterygoid hamulus and the synovial bursa of the TVP are identifiable. At week 9, the TVP is continuous with the palatine aponeurosis. At week 13, a connective tissue lamina appears between the TVP and the intramembranous ossification center for the anterior process of the malleus, which we know as the goniale and interpret as an attachment of the muscle to the primary vertebrate jaw or incudomalleal joint. The TVP from its origin, innervation and relation to the goniale appears to be a muscle of mastication that, at the end of the embryonic period, reaches the palatine aponeurosis anlage and the mesenchyme of the auditory tube and specializes in the movements of the soft palate and the auditory tube.     

Differential effects of stromal derived factor‐1α (SDF‐1α) on early and late stages of human megakaryocytic development

Stromal derived factor‐1α (SDF‐1α), the high‐affinity ligand of CXC‐chemokine receptor 4 (CXCR4), was added to human CD34⁺ hematopoietic progenitor cells that can be induced to differentiate along the monocytic or megakaryocytic lineages. In control liquid cell cultures supplemented with two different cytokine cocktails: stem cell factor (SCF), interleukin‐3 (IL‐3), macrophage‐colony stimulating factor (M‐CSF), and 10% fetal calf serum (FCS), or, SCF and thrombopoietin (TPO), the expression of surface CXCR4 progressively increased in both the CD14⁺ monocytic and CD41⁺ megakaryocytic lineages. While SDF‐1α caused only modest effects on cells of the monocytic lineage, it induced profound down‐regulation of CXCR4 in megakaryocytic cells at all stages of differentiation. Moreover, while SDF‐1α initially up‐regulated the early megakaryocytic antigen CD41, at later time points (days 12–16) it induced down‐regulation of the late megakaryocytic antigen CD42b. Consistently, at day 16, the number of mature megakaryocytes was significantly decreased in cultures supplemented with SDF‐1α. These findings indicate that, besides its primary role in regulating the retention of precursor cells in hematopoietic tissues, the SDF‐1α/CXCR4 system participates in the regulation of megakaryocytic development by stimulating the formation of immature megakaryoblasts and inhibiting the formation of mature megakaryocytes. Anat Rec 260:141–147, 2000. © 2000 Wiley‐Liss, Inc.     

Charles‐pierre denonvilliers (1808–1872): Renowned anatomist,plastic surgeon,and influential member of French society

Charles‐Pierre Denonvilliers was one of the most influential and prolific French anatomists and surgeons of the 19th century. Born in Paris and educated at the Paris Faculty of Medicine in 1826, he steadily created a reputation for himself in the field of medicine. Starting in 1833, Denonvilliers lectured with exquisite clarity and scientific accuracy in surgery and anatomy. Not only did he make a name for himself in this arena but also as an anatomist of high caliber based on his anatomical dissections and presentations. These talents and skills afforded Denonvilliers the opportunity to acquire different other titles and positions throughout his career. His reputation as a plastic surgeon, anatomist, and lecturer coupled with his status and influence made his sudden death in 1872, an occasion of bereavement for the French medical profession. Clin. Anat. 26:788–792, 2013. © 2012 Wiley Periodicals, Inc.     

Abnormalities of the der(12)t(12;21) in ETV6‐RUNX1 acute lymphoblastic leukemia

ETV6‐RUNX1 fusion [t(12;21)(p13;q22)] occurs in 25% of childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) and is associated with a favorable outcome. Additional abnormalities involving der(21)t(12;21) and nonrearranged chromosome 12 are well characterized but aberrations involving the der(12)t(12;21) have rarely been described. Herein, we describe two novel abnormalities affecting the der(12)t(12;21): a deletion (20/247, 8%) and duplication (10/247, 4%). All 30 patients were under 10 years of age, had a median white blood count of 12.4 × 10⁹/L and 19.2 × 10⁹/L, respectively, with a good outcome. Deletions of der(12)t(12;21) on both sides of the breakpoint were confirmed and mapped: centromeric (12p11.21‐12p13.2) and telomeric (21q22.12‐21q22.3). The size of these deletions extended from 0.4–13.4 to 0.8–2.5 Mb, respectively. The centromeric deletion encompassed the following genes: LRP6, BCL2L14, DUSP16, CREBL2, and CDKN1B. We postulate that this deletion occurs at the same time as the translocation because it was present in all ETV6–RUNX1‐positive cells. A second abnormality representing duplication of the reciprocal RUNX1–ETV6 fusion gene was a secondary event, which we hypothesize arose through mitotic recombination errors. This led to the formation of the following chromosome: der(12)(21qter→21q22.12::12 p13.2‐12 p12.3::12p12.3→12qter). Both abnormalities affect the reciprocal RUNX1–ETV6 fusion product which could either eliminate or amplify its expression and thus contribute to leukemogenesis. However, other consequences such as haploinsufficiency of tumor suppressor genes and amplification of oncogenes could also be driving forces behind these aberrations. In conclusion, this study has defined novel abnormalities in ETV6–RUNX1 BCP‐ALL, which implicate new genes involved in leukemogenesis. © 2012 Wiley Periodicals, Inc.     

Moritz Heinrich Romberg (1795–1873): Early founder of neurology

Moritz Heinrich Romberg (1795–1873) began his pursuit of neurology in 1820 by translating into German Andrew Marshall's The Morbid Anatomy of the Brain. In 1830, Romberg was hired as Privatdozent of special pathology and therapy in the Charité, the University Hospital of Berlin. He quickly rose to director of the royal clinic in 1845, at which time he wrote Lehrbuch der Nervenkrankheiten des Menschen, a text generally regarded as the first formal treatise on nervous diseases. He identified the role of proprioception in tabes dorsalis, and became the first neurologist to describe the typical pupillary presentation found in patients with tertiary syphilis. Romberg is perhaps most famous for identifying “Romberg's sign,” the distinctive sensory ataxia observed in neuropathies of the dorsal columns. Clin. Anat. 27:147–149, 2014. © 2012 Wiley Periodicals, Inc     

Growth of the human metatarsal bones in the fetal period (13–24 weeks postconception): a quantitative study

Summary We studied metatarsal growth in 600 metatarsal bones (60 pairs of feet) taken from 60 human fetuses (35 males and 25 females) ranging in age from 13 to 24 weeks postconception. The data obtained for the total length (TL) and for the ossified metatarsal length (OML) were correlated to fetal crown-rump length (C-R). The ossified metatarsal length presented a growth rate greater than the total length growth rate. There was no statistical difference between either the right and left metatarsals or males and females in total length and ossified metatarsal length growth during the period studied. We believe that metatarsal growth curves could be used to monitor fetal foot growth.

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Résumé Nous avons étudié la croissance métatarsienne sur 600 métatarsiens (60 paires de pieds) provenant de 60 foetus humains (35 masculins et 25 féminins) dont l'âge varie de 13 à 24 semaines après la conception. Les données concernant la Longueur Totale et la Longueur Osseuse ont été corrélées à la Longueur Vertex-Coccyx. La Longueur Osseuse a présenté un rythme de croissance plus rapide que la Longueur Totale. Il n'y avait pas de différences significatives pour la croissance de la Longueur Osseuse ou de la Longueur Totale ni entre les métatarsiens droits et gauches, ni entre les foetus masculins et féminins durant la période étudiée. Nous pensons que les courbes de croissance métarsienne pourraient être utilisées pour suivre la croissance du pied fetal.

     

High resolution three-dimensional imaging and measurement of lung,heart, liver,and diaphragmatic development in the fetal rat based on micro-computed tomography (micro-CT)

Understanding of normal fetal organ development is crucial for the evaluation of the pathogenesis of congenital anomalies. Various techniques have been used to generate imaging of fetal rat organogenesis, such as histological dissection with 3-dimensional reconstruction and scanning electron microscopy. However, these techniques did not imply quantitative measurements of developing organs (volumes, surface areas of organs). Furthermore, a partial or total destruction of the embryos prior to analysis was inevitable. Recently, micro-computed tomography (micro-CT) has been established as a novel tool to investigate embryonic development in non-dissected embryos of rodents. In this study, we used the micro-CT technique to generate 4D datasets of rat embryos aged between embryonic day 15–22 and newborns. Lungs, hearts, diaphragms, and livers were digitally segmented in order to measure organ volumes and analyze organ development as well as generate high-resolution 3D images. These data provide objective values compiling a 4D atlas of pulmonary, cardiac, diaphragmatic, and hepatic development in the fetal rat.     

Francesco Parona (1842–1908) and his contributions to our understanding of surgery through anatomy

Much of the life of Francesco Parona and many of his contributions to medicine are unknown outside of Europe. Parona made novel contributions to many surgical techniques and medical treatments and was an active member of society and the Italian political regime. Parona's name lives on eponymously by his “space” in the forearm. This paper will discuss the personal life and medical contributions of Francesco Parona. Clin. Anat. 26:547–550, 2013. © 2012 Wiley Periodicals, Inc.     

A staging table for the embryonic development of the brownbanded bamboo shark (Chiloscyllium punctatum)

Background: Studying cartilaginous fishes (chondrichthyans) has helped us understand vertebrate evolution and diversity. However, resources such as genome sequences, embryos, and detailed staging tables are limited for species within this clade. To overcome these limitations, we have focused on a species, the brownbanded bamboo shark (Chiloscyllium punctatum), which is a relatively common aquarium species that lays eggs continuously throughout the year. In addition, because of its relatively small genome size, this species is promising for molecular studies. Results: To enhance biological studies of cartilaginous fishes, we establish a normal staging table for the embryonic development of the brownbanded bamboo shark. Bamboo shark embryos take around 118 days to reach the hatching period at 25°C, which is approximately 1.5 times as fast as the small‐spotted catshark (Scyliorhinus canicula) takes. Our staging table divides the embryonic period into 38 stages. Furthermore, we found culture conditions that allow early embryos to grow in partially opened egg cases. Conclusions: In addition to the embryonic staging table, we show that bamboo shark embryos exhibit relatively fast embryonic growth and are amenable to culture, key characteristics that enhance their experimental utility. Therefore, the present study is a foundation for cartilaginous fish research. Developmental Dynamics 247:712–723, 2018. © 2017 Wiley Periodicals, Inc.