The development of the external genitals in female human embryos and foetuses. Part 2: Vaginal vestibule, anal canal, perineal raphe and perineal cutaneous muscles.

Concomitant with the rupture of the cloacal membrane, the perineal skin epithelium thickens (see accompanying article). In this study, we establish in female embryos and foetuses that the thick skin area divides into ventral and dorsal areas at ~14 weeks and gradually becomes restricted to the vaginal vestibule and anal canal thereafter. The dense mesenchymal core of the labia minora, which forms at ~8 weeks, extends dorsally to the anal canal as a midline reinforcement. The skin epithelium overlying this reinforcement is much thinner than the flanking 'thick skin', and is supported by an interrupted basement membrane, which implies epithelial-mesenchymal transformation of the thin midline epithelium and the subsequent establishment of the perineal raphe by the merging of the adjacent thick epithelium. Meanwhile, the anogenital distance in the perineum increases rapidly in length. Perhaps as a consequence, the labia minora cover only the ventral third of the vaginal vestibule at 20 weeks. The endodermal ducts of Bartholin's glands are identifiable at 7 weeks, while acini form at ~12 weeks. The vestibular bulbs become identifiable at ~10 weeks and form vascular networks after ~14.5 weeks. After the rupture of the cloacal membrane, the diameter of the junction of the dorsal cloaca with the anal canal is just a pinhole but widens dorsoventrally after the 7th week. The cutaneous muscles of the perineal area form as a ventrally open U-shaped mesenchymal mass, from which the anal sphincter and bulbospongiosus muscle develop. In conclusion, our findings show that thick skin epithelium persists in the vaginal vestibule and anal canal.

The development of the external genitals in female human embryos and foetuses. Part 1: Perineal thick skin, clitoris and labia.

Concomitant with the rupture of the cloacal membrane in the 6th week of development, the intermediate layer of the perineal-skin epithelium thickens. We investigated its distribution and the development of the corresponding subcutaneous compartments in serial sections of female human embryos and foetuses and prepared 3D reconstructions to establish topographic relations. The thick-skin area becomes restricted to the outlets of the genital and intestinal tracts. The clitoris and labia majora become identifiable at ~7 weeks. The mesenchymal mass inside the clitoris soon divides into the glans and the cavernous bodies. The clitoral hood forms between 10 and 14 weeks as a fold of tissue that extends from proximal to distal over the glans. Due to the caudal bending of the clitoral shaft, the labia majora gradually cover the clitoris after ~14 weeks. The labia minora form at ~8 weeks from the ridges of thick-skin epithelium that flank the genital exit. They are continuous ventrolaterally with the clitoral hood and ventromedially with the apex of the cavernous body. Dorsally, their dense subcutaneous mesenchymal core extends to the anal canal. Between 8 and 14 weeks, the urethra lengthens axially, while the vaginal vestibule extends ventrally. In this period, the urethral plate of female embryos is mitotically active but does not increase in volume, which suggests that it contributes to vestibular growth. In conclusion, we observed a temporal correlation between the development of the thick-skin epithelium and that of the external genitals, with a distribution that is reminiscent of the dihydrotestosterone-sensitive skin.

Human Cardiac Development.

Many aspects of heart development are topographically complex and require three-dimensional (3D) reconstruction to understand the pertinent morphology. We have recently completed a comprehensive primer of human cardiac development that is based on firsthand segmentation of structures of interest in histological sections. We visualized the hearts of 12 human embryos between their first appearance at 3.5 weeks and the end of the embryonic period at 8 weeks. The models were presented as calibrated, interactive, 3D portable document format (PDF) files. We used them to describe the appearance and the subsequent remodeling of around 70 different structures incrementally for each of the reconstructed stages. In this chapter, we begin our account by describing the formation of the single heart tube, which occurs at the end of the fourth week subsequent to conception. We describe its looping in the fifth week, the formation of the cardiac compartments in the sixth week, and, finally, the septation of these compartments into the physically separated left- and right-sided circulations in the seventh and eighth weeks. The phases are successive, albeit partially overlapping. Thus, the basic cardiac layout is established between 26 and 32 days after fertilization and is described as Carnegie stages (CSs) 9 through 14, with development in the outlet component trailing that in the inlet parts. Septation at the venous pole is completed at CS17, equivalent to almost 6 weeks of development. During Carnegie stages 17 and 18, in the seventh week, the outflow tract and arterial pole undergo major remodeling, including incorporation of the proximal portion of the outflow tract into the ventricles and transfer of the spiraling course of the subaortic and subpulmonary channels to the intrapericardial arterial trunks. Remodeling of the interventricular foramen, with its eventual closure, is complete at CS20, which occurs at the end of the seventh week. We provide quantitative correlations between the age of human and mouse embryos as well as the Carnegie stages of development. We have also set our descriptions in the context of variations in the timing of developmental features.

Anatomical study and meta-analysis of the episternal ossicles.

Episternal ossicles (EO) are accessory bones located superior and posterior to the manubrium, representing an anatomical variation in the thoracic region. This study aimed to investigate the prevalence and developmental aspects of EO in global populations. The prevalence of EO in pediatric populations was assessed using the "Pediatric-CT-SEG" open-access data set obtained from The Cancer Imaging Archive, revealing a single incidence of EO among 233 subjects, occurring in a 14-year-old patient. A meta-analysis was conducted using data from 16 studies (from 14 publications) through three electronic databases (Google Scholar, PubMed, and Journal Storage) encompassing 7997 subjects. An overall EO prevalence was 2.1% (95% CI 1.1-3.0%, I2 = 93.75%). Subgroup analyses by continent and diagnostic methods were carried out. Asia exhibited the highest prevalence of EO at 3.8% (95% CI 0.3-7.5%, I2 = 96.83%), and X-ray yielded the highest prevalence of 0.7% (95% CI 0.5-8.9%, I2 = 0.00%) compared with other modalities. The small-study effect was indicated by asymmetric funnel plots (Egger's z = 4.78, p < 0.01; Begg's z = 2.30, p = 0.02). Understanding the prevalence and developmental aspects of EO is crucial for clinical practitioners' awareness of this anatomical variation.

The thyroid foramen: a systematic review and meta-analysis.

PURPOSE: To systematically review published studies on the prevalence of the thyroid foramen (TF), perform a meta-analysis to generate pooled prevalence estimates, and identify factors associated with its presence. METHODS: A systematic literature search was conducted in Google Scholar, PubMed, and Journal Storage databases. Studies reporting the prevalence of the thyroid foramen were included without language or date restrictions. Quality assessment was performed using AQUA tool. A random-effects meta-analysis was performed with subgroup analyses. Heterogeneity was assessed using Higgins' I2 statistics, and publication bias was evaluated using funnel plots and Egger's test. RESULTS: Out of 271 entries, 38 studies met the inclusion criteria, comprising 3,030 subjects from various continents. The overall TF prevalence was 24.5% (95% CI: 19.2-29.8%, I2 = 93.44%), with unilateral TF present in 16.9% and bilateral TF in 6.2%. Prevalence was highest in North America (31.4%,) and lowest in Africa (12.3%). No significant prevalence difference was found between adults and younger populations (p = 0.15). Publication bias, or the small-study effect, was detected (p < 0.01). CONCLUSION: This meta-analysis reveals a 24.5% overall prevalence of TF, with significant heterogeneity primarily explained by geographical differences. The TF's clinical relevance necessitates awareness among surgeons and radiologists to avoid complications during laryngeal surgeries and prevent misdiagnosis in imaging studies.

Accessory extensor pollicis longus from the extensor digitorum: a rare case report and review of the literature.

PURPOSE: Variations of the extensor pollicis longus are rare. When present, these include a separate extensor pollicis longus muscle, tendon or an intertendinous connection with nearby tendons within the deep extensor compartment of the forearm. Here, we report an extremely rare variation of an accessory extensor pollicis longus originating from the extensor digitorum. METHODS: An unusual muscle was found during the routine dissection forearm of a 71 year-old at death male cadaver. RESULTS: This variant muscle originated from part of the extensor digitorum muscle belly that supplies the index finger. It became tendinous and entered the third extensor compartment of the wrist before joining the ulnar side of the extensor pollicis longus tendon. Traction on the muscle belly resulted in simultaneous extension of both the thumb and the index finger. CONCLUSION: This study documents an extremely rare extensor tendon to the thumb originating from the extensor digitorum, with a unique attachment to the normal extensor pollicis tendon. There have been minimal accounts of this variation, and the present report adds to the limited literature. Furthermore, the report suggests a new subtype, 1f, be included in the existing classification system. Surgeons should be aware of this rare variant for proper evaluation, diagnosis and surgical treatment. Further anatomical studies are needed to study the prevalence of this variant.

Anatomical Variants Identified on Computed Tomography of Oropharyngeal Carcinoma Patients.

Background and Objectives: Anatomical variations in the head, neck and chest are common, and are observed as occasional findings on computed tomography (CT). Although anatomical variations are mostly asymptomatic and do not cause any negative influence on the body function, they may jeopardize diagnosis and may be confused with pathological conditions. The presence of variations may also limit surgical access during tumor removal. The aim of this study was to investigate the prevalence of six anatomical variations-os acromiale, episternal ossicles, cervical rib, Stafne bone cavity, azygos lobe and tracheal bronchus-in an open-access computed tomography dataset obtained from oropharyngeal cancer patients. Materials and Methods: A total of 606 upper-chest and neck computed-tomography scans (79.4% male and 20.6% female) were retrospectively investigated. Sex difference was evaluated using the z-test for two proportions. Results: Os acromiale, episternal ossicles, cervical rib, Stafne bone cavity, azygos lobe, and tracheal bronchus were present in 3.1%, 2.2%, 0.2%, 0%, 0.3% and 0.5%, respectively, of all patients. Os acromiale was identified as meso-acromion in 86.6%, and as pre-acromion in 17.4%, of all acromia. Episternal ossicles were present unilaterally in 58.3%, and bilaterally in 41.7%, of all sterna. Only the cervical rib showed a sex difference in prevalence. Conclusions: awareness of these variations is important for radiologists interpreting head, neck and chest CTs; for example, those of oropharyngeal cancer patients. This study also illustrates the applicability of publicly available datasets in prevalence-based anatomical research. While most of the variations investigated in the present study are well-known, the episternal ossicles are not well explored, and need further investigation.

Anatomical variants identified on chest computed tomography of 1000+ COVID-19 patients from an open-access dataset.

Chest computed tomography (CT) has been the preferred imaging modality during the pandemic owing to its sensitivity in detecting COVID-19 infections. Recently, a large number of COVID-19 imaging datasets have been deposited in public databases, leading to rapid advances in COVID-19 research. However, the application of these datasets beyond COVID-19-related research has been little explored. The authors believe that they could be used in anatomical research to elucidate the link between anatomy and disease and to study disease-related alterations to normal anatomy. Therefore, the present study was designed to investigate the prevalence of six well-known anatomical variants in the thorax using open-access CT images obtained from over 1000 Iranian COVID-19 patients aged between 6 and 89 years (60.9% male and 39.1% female). In brief, we found that the azygos lobe, tracheal bronchus, and cardiac bronchus were present in 0.8%, 0.2%, and 0% of the patients, respectively. Variations of the sternum, including sternal foramen, episternal ossicles, and sternalis muscle, were observed in 9.6%, 2.9%, and 1.5%, respectively. We believe anatomists could benefit from using open-access datasets as raw materials for research because these datasets are freely accessible and are abundant, though further research is needed to evaluate the uses of other datasets from different body regions and imaging modalities. Radiologists should also be aware of these common anatomical variants when examining lung CTs, especially since the use of this imaging modality has increased during the pandemic.

A reverse form of Linburg-Comstock variation with comments on its etiology and demonstration of interactive 3D portable document format.

PURPOSE: Two most common variations of flexor pollicis longus include its accessory head and its connection with the flexor digitorum profundus of the index (Linburg-Comstock variation). In addition, while three-dimensional (3D) screening has widely been used in anatomical education, its use as reporting tool in anatomical research is still limited. The objective of this study is to report a previously unrecognized form of the accessory head of flexor pollicis longus, discuss the potential etiology of Linburg-Comstock variation, and pilot the 3D scanning of a large-scale anatomical structure. METHODS: An unusual tendon slip was discovered during a routine dissection in the anterior compartment of the right forearm of a 54-year-old male cadaver. A 3D scanner was used to capture the surface topography of the specimen and an interactive portable document format (PDF) was created. RESULTS: An anomalous tendon was found originating from the lateral aspect of the flexor digitorum profundus muscle. This variant tendon then inserted onto the medial surface of the flexor pollicis longus tendon before entering the carpal tunnel. The variation resembles a reverse form of Linburg-Comstock variation, because pulling this variant tendon resulted in simultaneous flexion of the interphalangeal joint of thumb. CONCLUSION: Surgeons should be aware of the reverse Linburg-Comstock variation, because it may not be detectable by the conventional provocative testing. Linburg-Comstock variation may be classified as an anatomical variant or a secondarily acquired condition depending on its type. Our demonstration of interactive 3D-PDF file highlights its potential use for delivering anatomical information in future cadaveric studies.

Cross-Sectional Area of the Tibial Nerve in Diabetic Peripheral Neuropathy Patients: A Systematic Review and Meta-Analysis of Ultrasonography Studies.

Background: There is a link between diabetic peripheral neuropathy (DPN) progression and the increase in the cross-sectional area (CSA) of the tibial nerve at the ankle. Nevertheless, no prior meta-analysis has been conducted to evaluate its usefulness for the diagnosis of DPN. Methods: We searched Google Scholar, Scopus, and PubMed for potential studies. Studies had to report tibial nerve CSA at the ankle and diabetes status (DM, DPN, or healthy) to be included. A random-effect meta-analysis was applied to calculate pooled tibial nerve CSA and mean differences across the groups. Subgroup and correlational analyses were conducted to study the potential covariates. Results: The analysis of 3295 subjects revealed that tibial nerve CSA was 13.39 mm2 (CI: 10.94−15.85) in DM patients and 15.12 mm2 (CI: 11.76−18.48) in DPN patients. The CSA was 1.93 mm2 (CI: 0.92−2.95, I2 = 98.69%, p < 0.01) larger than DPN-free diabetic patients. The diagnostic criteria of DPN and age were also identified as potential moderators of tibial nerve CSA. Conclusions: Although tibial nerve CSA at the ankle was significantly larger in the DPN patients, its clinical usefulness is limited by the overlap between groups and the inconsistency in the criteria used to diagnose DPN.

The development of the dorsal mesentery in human embryos and fetuses.

The vertebrate intestine has a continuous dorsal mesentery between pharynx and anus that facilitates intestinal mobility. Based on width and fate the dorsal mesentery can be subdivided into that of the caudal foregut, midgut, and hindgut. The dorsal mesentery of stomach and duodenum is wide and topographically complex due to strong and asymmetric growth of the stomach. The associated formation of the lesser sac partitions the dorsal mesentery into the right-sided "caval fold" that serves as conduit for the inferior caval vein and the left-sided mesogastrium. The thin dorsal mesentery of the midgut originates between the base of the superior and inferior mesenteric arteries, and follows the transient increase in intestinal growth that results in small-intestinal looping, intestinal herniation and, subsequently, return. The following fixation of a large portion of the abdominal dorsal mesentery to the dorsal peritoneal wall by adhesion and fusion is only seen in primates and is often incomplete. Adhesion and fusion of mesothelial surfaces in the lesser pelvis results in the formation of the "mesorectum". Whether Toldt's and Denonvilliers' "fasciae of fusion" identify the location of the original mesothelial surfaces or, alternatively, represent the effects of postnatal wear and tear due to intestinal motility and intra-abdominal pressure changes, remains to be shown. "Malrotations" are characterized by growth defects of the intestinal loops with an ischemic origin and a narrow mesenteric root due to insufficient adhesion and fusion.

Development of the sympathetic trunks in human embryos.

Although the development of the sympathetic trunks was first described >100 years ago, the topographic aspect of their development has received relatively little attention. We visualised the sympathetic trunks in human embryos of 4.5-10 weeks post-fertilisation, using Amira 3D-reconstruction and Cinema 4D-remodelling software. Scattered, intensely staining neural crest-derived ganglionic cells that soon formed longitudinal columns were first seen laterally to the dorsal aorta in the cervical and upper thoracic regions of Carnegie stage (CS)14 embryos. Nerve fibres extending from the communicating branches with the spinal cord reached the trunks at CS15-16 and became incorporated randomly between ganglionic cells. After CS18, ganglionic cells became organised as irregular agglomerates (ganglia) on a craniocaudally continuous cord of nerve fibres, with dorsally more ganglionic cells and ventrally more fibres. Accordingly, the trunks assumed a "pearls-on-a-string" appearance, but size and distribution of the pearls were markedly heterogeneous. The change in position of the sympathetic trunks from lateral (para-aortic) to dorsolateral (prevertebral or paravertebral) is a criterion to distinguish the "primary" and "secondary" sympathetic trunks. We investigated the position of the trunks at vertebral levels T2, T7, L1 and S1. During CS14, the trunks occupied a para-aortic position, which changed into a prevertebral position in the cervical and upper thoracic regions during CS15, and in the lower thoracic and lumbar regions during CS18 and CS20, respectively. The thoracic sympathetic trunks continued to move further dorsally and attained a paravertebral position at CS23. The sacral trunks retained their para-aortic and prevertebral position, and converged into a single column in front of the coccyx. Based on our present and earlier morphometric measurements and literature data, we argue that differential growth accounts for the regional differences in position of the sympathetic trunks.

The prevalence of the azygos lobe: A meta-analysis of 1,033,083 subjects.

The azygos lobe (AL) is an accessory lobe of the right lung with prevalence between 0.4 and 1.2%. The aim of the present review is to provide a better estimate of the frequency of the AL and to examine its relationships with other variables such as population, diagnostic methods, and co-occurring illnesses. Studies published between 1899 and October 2020 were searched through three electronic databases; Google Scholar, PubMed, and JSTOR. Titles, abstracts, and full texts of the retrieved entries were screened to determine their appropriateness for inclusion. A total of 88 studies relating to 1,033,083 subjects met the inclusion criteria. A random-effects meta-analysis yielded an overall prevalence of 0.30% (95% CI: 0.0024-0.0035, I2  = 97.9%). Linear regression and subgroup analysis revealed a negative correlation (ρ = -0.540, p <0.001) between AL prevalence and sample size; studies with smaller sample sizes had higher prevalences. The AL prevalence in individuals with congenital pulmonary defects, 5.2% (95% CI: 0.0018-0.0086, I2  = 0%), was 17 times higher than the overall prevalence (z = 6.65, p <0.001), suggesting associations with other abnormalities and possibly a genetic predisposition. In addition to an evidence-based synthesis of AL prevalence, this study demonstrates publication bias and small-study effects in the anatomy literature. Awareness of the AL is crucial for radiologists when they interpret unusual radiological findings and for surgeons when they operate in the region.

Extrinsic innervation of the pelvic organs in the lesser pelvis of human embryos.

Realistic models to understand the developmental appearance of the pelvic nervous system in mammals are scarce. We visualized the development of the inferior hypogastric plexus and its preganglionic connections in human embryos at 4-8 weeks post-fertilization, using Amira 3D reconstruction and Cinema 4D-remodelling software. We defined the embryonic lesser pelvis as the pelvic area caudal to both umbilical arteries and containing the hindgut. Neural crest cells (NCCs) appeared dorsolateral to the median sacral artery near vertebra S1 at ~5 weeks and had extended to vertebra S5 1 day later. Once para-arterial, NCCs either formed sympathetic ganglia or continued to migrate ventrally to the pre-arterial region, where they formed large bilateral inferior hypogastric ganglionic cell clusters (IHGCs). Unlike more cranial pre-aortic plexuses, both IHGCs did not merge because the 'pelvic pouch', a temporary caudal extension of the peritoneal cavity, interposed. Although NCCs in the sacral area started to migrate later, they reached their pre-arterial position simultaneously with the NCCs in the thoracolumbar regions. Accordingly, the superior hypogastric nerve, a caudal extension of the lumbar splanchnic nerves along the superior rectal artery, contacted the IHGCs only 1 day later than the lumbar splanchnic nerves contacted the inferior mesenteric ganglion. The superior hypogastric nerve subsequently splits to become the superior hypogastric plexus. The IHGCs had two additional sources of preganglionic innervation, of which the pelvic splanchnic nerves arrived at ~6.5 weeks and the sacral splanchnic nerves only at ~8 weeks. After all preganglionic connections had formed, separate parts of the inferior hypogastric plexus formed at the bladder neck and distal hindgut.

Development of extrinsic innervation in the abdominal intestines of human embryos.

Compared to the intrinsic enteric nervous system (ENS), development of the extrinsic ENS is poorly documented, even though its presence is easily detectable with histological techniques. We visualised its development in human embryos and foetuses of 4-9.5 weeks post-fertilisation using Amira 3D-reconstruction and Cinema 4D-remodelling software. The extrinsic ENS originated from small, basophilic neural crest cells (NCCs) that migrated to the para-aortic region and then continued ventrally to the pre-aortic region, where they formed autonomic pre-aortic plexuses. From here, nerve fibres extended along the ventral abdominal arteries and finally connected to the intrinsic system. Schwann cell precursors (SCPs), a subgroup of NCCs that migrate on nerve fibres, showed region-specific differences in differentiation. SCPs developed into scattered chromaffin cells of the adrenal medulla dorsolateral to the coeliac artery (CA) and into more tightly packed chromaffin cells of the para-aortic bodies ventrolateral to the inferior mesenteric artery (IMA), with reciprocal topographic gradients between both fates. The extrinsic ENS first extended along the CA and then along the superior mesenteric artery (SMA) and IMA 5 days later. Apart from the branch to the caecum, extrinsic nerves did not extend along SMA branches in the herniated parts of the midgut until the gut loops had returned in the abdominal cavity, suggesting a permissive role of the intraperitoneal environment. Accordingly, extrinsic innervation had not yet reached the distal (colonic) loop of the midgut at 9.5 weeks development. Based on intrinsic ENS-dependent architectural remodelling of the gut layers, extrinsic innervation followed intrinsic innervation 3-4 Carnegie stages later.

The development of the cloaca in the human embryo.

Subdivision of cloaca into urogenital and anorectal passages has remained controversial because of disagreements about the identity and role of the septum developing between both passages. This study aimed to clarify the development of the cloaca using a quantitative 3D morphological approach in human embryos of 4-10 post-fertilisation weeks. Embryos were visualised with Amira 3D-reconstruction and Cinema 4D-remodelling software. Distances between landmarks were computed with Amira3D software. Our main finding was a pronounced difference in growth between rapidly expanding central and ventral parts, and slowly or non-growing cranial and dorsal parts. The entrance of the Wolffian duct into the cloaca proved a stable landmark that remained linked to the position of vertebra S3. Suppressed growth in the cranial cloaca resulted in an apparent craniodorsal migration of the entrance of the Wolffian duct, while suppressed growth in the dorsal cloaca changed the entrance of the hindgut from cranial to dorsal on the cloaca. Transformation of this 'end-to-end' into an 'end-to-side' junction produced temporary 'lateral (Rathke's) folds'. The persistent difference in dorsoventral growth straightened the embryonic caudal body axis and concomitantly extended the frontally oriented 'urorectal (Tourneux's) septum' caudally between the ventral urogenital and dorsal anorectal parts of the cloaca. The dorsoventral growth difference also divided the cloacal membrane into a well-developed ventral urethral plate and a thin dorsal cloacal membrane proper, which ruptured at 6.5 weeks. The expansion of the pericloacal mesenchyme followed the dorsoventral growth difference and produced the genital tubercle. Dysregulation of dorsal cloacal development is probably an important cause of anorectal malformations: too little regressive development may result in anorectal agenesis, and too much regression in stenosis or atresia of the remaining part of the dorsal cloaca.

Closure of the vertebral canal in human embryos and fetuses.

The vertebral column is the paradigm of the metameric architecture of the vertebrate body. Because the number of somites is a convenient parameter to stage early human embryos, we explored whether the closure of the vertebral canal could be used similarly for staging embryos between 7 and 10 weeks of development. Human embryos (5-10 weeks of development) were visualized using Amira 3D® reconstruction and Cinema 4D® remodelling software. Vertebral bodies were identifiable as loose mesenchymal structures between the dense mesenchymal intervertebral discs up to 6 weeks and then differentiated into cartilaginous structures in the 7th week. In this week, the dense mesenchymal neural processes also differentiated into cartilaginous structures. Transverse processes became identifiable at 6 weeks. The growth rate of all vertebral bodies was exponential and similar between 6 and 10 weeks, whereas the intervertebral discs hardly increased in size between 6 and 8 weeks and then followed vertebral growth between 8 and 10 weeks. The neural processes extended dorsolaterally (6th week), dorsally (7th week) and finally dorsomedially (8th and 9th weeks) to fuse at the midthoracic level at 9 weeks. From there, fusion extended cranially and caudally in the 10th week. Closure of the foramen magnum required the development of the supraoccipital bone as a craniomedial extension of the exoccipitals (neural processes of occipital vertebra 4), whereas a growth burst of sacral vertebra 1 delayed closure until 15 weeks. Both the cranial- and caudal-most vertebral bodies fused to form the basioccipital (occipital vertebrae 1-4) and sacrum (sacral vertebrae 1-5). In the sacrum, fusion of its so-called alar processes preceded that of the bodies by at least 6 weeks. In conclusion, the highly ordered and substantial changes in shape of the vertebral bodies leading to the formation of the vertebral canal make the development of the spine an excellent, continuous staging system for the (human) embryo between 6 and 10 weeks of development.

The fate of the vitelline and umbilical veins during the development of the human liver.

Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo.

Complete transverse basilar cleft associated with hemifacial microsomia.

Transverse basilar cleft (TBC) is an extremely rare variation of the clivus or the basilar part of the occipital bone. In this report, a unilateral transverse basilar fissure was found at the clivus in a head computed tomography of an 18-year-old female patient diagnosed with hemifacial microsomia (HFM). Image analysis of this patient showed shortening of the ramus of the right mandible along with medial displacement of the right temporomandibular joint and hypoplastic right maxilla. In addition, observation of the clivus showed a cleft between the basioticum and basioccipital bones at the level of the pharyngeal tubercle on the right side. This cleft was identified as TBC. Clival variations, TBC included, attributed to HFM have never been reported. This report draws attention to the complex relationship between abnormal development of clivus and HFM syndrome, and sheds light on a possible genetic and molecular association between these two conditions.