Head‐turning morphologies: Evolution of shape diversity in the mammalian atlas–axis complex

Mammals flex, extend, and rotate their spines as they perform behaviors critical for survival, such as foraging, consuming prey, locomoting, and interacting with conspecifics or predators. The atlas–axis complex is a mammalian innovation that allows precise head movements during these behaviors. Although morphological variation in other vertebral regions has been linked to ecological differences in mammals, less is known about morphological specialization in the cervical vertebrae, which are developmentally constrained in number but highly variable in size and shape. Here, we present the first phylogenetic comparative study of the atlas–axis complex across mammals. We used spherical harmonics to quantify 3D shape variation of the atlas and axis across a diverse sample of species, and performed phylogenetic analyses to investigate if vertebral shape is associated with body size, locomotion, and diet. We found that differences in atlas and axis shape are partly explained by phylogeny, and that mammalian subclades differ in morphological disparity. Atlas and axis shape diversity is associated with differences in body size and locomotion; large terrestrial mammals have craniocaudally elongated vertebrae, whereas smaller mammals and aquatic mammals have more compressed vertebrae. These results provide a foundation for investigating functional hypotheses underlying the evolution of neck morphologies across mammals.     

Patterns of growth in the presacral vertebral column of the leopard gecko (Eublepharis macularius)

Postnatal growth patterns within the vertebral column may be informative about body proportions and regionalization. We measured femur length, lengths of all pre‐sacral vertebrae, and lengths of intervertebral spaces, from radiographs of a series of 21 Eublepharis macularius, raised under standard conditions and covering most of the ontogenetic body size range. Vertebrae were grouped into cervical, sternal, and dorsal compartments, and lengths of adjacent pairs of vertebrae were summed before analysis. Femur length was included as an index of body size. Principal component analysis of the variance‐covariance matrix of these data was used to investigate scaling among them. PC1 explained 94.19% of total variance, interpreted as the variance due to body size. PC1 differed significantly from the hypothetical isometric vector, indicating overall allometry. The atlas and axis vertebrae displayed strong negative allometry; the remainder of the vertebral pairs exhibited weak negative allometry, isometry or positive allometry. PC1 explained a markedly smaller amount of variance for the vertebral pairs of the cervical compartment than for the remainder of the vertebral pairs, with the exception of the final pair. The relative standard deviations of the eigenvalues from the PCAs of the three vertebral compartments indicated that the vertebrae of the cervical compartment were less strongly integrated by scaling than were the sternal or dorsal vertebrae, which did not differ greatly between themselves in their strong integration, suggesting that the growth of the cervical vertebrae is constrained by the mechanical requirements of the head. Regionalization of the remainder of the vertebral column is less clearly defined but may be associated with wave form propagation incident upon locomotion, and by locomotory changes occasioned by tail autotomy and regeneration. Femur length exhibits negative allometry relative to individual vertebral pairs and to vertebral column length, suggesting a change in locomotor requirements over the ontogenetic size range.     

太行山猕猴寰椎和枢椎的初步研究

对成年太行山猕猴寰椎和枢椎变量进行了测量;以肱骨最大长为参照,对其变量进行了异速生长分析。结果表明：寰椎全宽及枢椎椎孔横径接近等速生长,其余变量均为负异速生长。     

Embryonic development of the human duodenum

Epithelial duodenal anlage takes place at the end of the first month of the human embryogenesis in connection with appearance of the pancreatic epithelial germs. It has a form of a short arch with a spindle-like enlargement of the middle ductal part. Formation of the hepato-duodenal ligament and of the duodenal mesentery results in appearance of the given organ anlage with a three-layered wall in 5.5-6-week-old embryos. The anlage makes an arch, protruding to the right and forward with a spindle-like enlargement of the middle ductal part. It is tightly connected with the forming anlage of the pancreatic head, when the pancreatic epithelial anlages are fusing. An intensive growth of the pancreatic head is accompanied with emergence and enlargement of the superior, descending and inferior parts of the duodenum, that acquires a semicircular form in 8-8.5-week-old embryos. Its transitional stage is a curved semicircle having a form of a distended spiral coil; that reflects an uneven growth of the organ in the human embryogenesis.     

The elongation of the human cervical vertebral column

Cervical vertebral elongation has been studied using serial cephalometric radiographs of 32 children examined regularly from 0.25 to 17 years. Mean vertebral body heights increased rapidly to about 2.5 years and then decelerated except for a spurt at about the age of peak height velocity. There were only small sex differences in vertebral body elongation to 12 years. From then to 15 years, the vertebral body heights in the girls exceeded those in the boys; later this sex difference was reversed. There was no pubertal spurt in disc elongation. The correlation coefficients were negative between vertebral body heights and the heights of adjoining intervertebral discs, e.g., body C3 and disc C3–4, but those between body heights or between disc heights were positive. The heights of adjacent cervical vertebral bodies were correlated more highly than the heights of non-adjacent bodies. There was a similar pattern of differences between correlation coefficients for the heights of adjacent and non-adjacent intervertebral discs.     

The human secretome atlas initiative: Implications in health and disease conditions

Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts toward secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study. This article is part of a Special Issue entitled: An Updated Secretome.     

Vertebral morphology of Nacholapithecus kerioi based on KNM-BG 35250

This paper describes the morphology of the vertebral remains of the KNM-BG 35250 Nacholapithecus kerioi individual from the Middle Miocene of Kenya. Cervical vertebrae are generally large relative to presumed body mass, suggesting a heavy head with large jaws and well-developed neck muscles. The atlas retains the lateral and posterior bridges over the vertebral artery. The axis has a robust dens and a large angle formed by superior articular surfaces. The thoracic vertebral specimens include the diaphragmatic vertebra and one post-diaphragmatic vertebra. The thoracic vertebral bodies are much smaller that those of male Papio cynocephalus, whereas many of the dorsal elements are large and robust, exceeding those of male P. cynocephalus. Lumbar vertebral bodies are small relative to body mass, craniocaudally moderately long, and have a median ventral keel. The transverse process is craniocaudally long and arises from the widest part of the body cranially and the pedicle above the inferior vertebral notch caudally. Anapophyses are present in one of the preserved lumbar vertebrae. The postzygapophyses are thick dorsoventrally. These lumbar features are broadly shared with Proconsul. However, the base of the spinous process is longer and more caudally positioned in N. kerioi compared to Proconsul, and is more similar to the condition in Pongo. They are not dorsally (or moderately caudally) directed as is seen in P. nyanzae, Pan, and most other extant primates. A caudally directed spinous process does not permit a broad range of spinal dorsiflexion. The presumed stiff back in N. kerioi suggests a different locomotor repertoire than in Proconsul. Morotopithecus bishopi, although not possessing the same features, exhibits another morphological suite of characters for lumbar stiffness. Diverse functional adaptations of the lumbar spine were present in African hominoids during the Early to Middle Miocene.     

Ligament insertions into the human lumbar vertebral body.

The insertion of the annulus fibrosus and of the perivertebral ligaments into the lumbar vertebral body is studied by histology and microradiography, in post-mortem human material from 0 to 34 years of age. The annulus lamellosus is attached to the edge ring, whose origin is endochondral, and ends in a calcified cartilage. The perivertebral ligaments are fixed to the cortex, that derives from those ligaments; they join the vertebral body via bundle bone.     

Some observations on the posterior and lateral bridge of the atlas

Six hundred and seventy-two atlas vertebrae of 6 population groups were examined for the presence of a posterior and/or lateral bridge. Of these, 174 (25.9%) presented with partial posterior bridge formation and 53 (7.9%) with a complete bridge. Twenty-six (3.8%) showed some form of lateral bridging. Although controversy exists as to the origin of atlas bridging, the findings of the present study show that aging could be a factor predisposing to complete bridge formation. The clinical significance of bridge formation is discussed with reference to their possible effect on normal vertebral artery function, particularly in rotation.     

Differential segmental growth of the vertebral column of the rat (Rattus norvegicus)

Despite the pervasive occurrence of segmental morphologies in the animal kingdom, the study of segmental growth is almost entirely lacking, but may have significant implications for understanding the development of these organisms. We investigate the segmental and regional growth of the entire vertebral column of the rat (Rattus norvegicus) by fitting a Gompertz curve to length and age data for each vertebra and each vertebral region. Regional lengths are calculated by summing constituent vertebral lengths and intervertebral space lengths for cervical, thoracic, lumbar, sacral, and caudal regions. Gompertz curves allow for the estimation of parameters representing neonatal and adult vertebral and regional lengths, as well as initial growth rate and the rate of exponential growth decay. Findings demonstrate differences between neonatal and adult rats in terms of relative vertebral lengths, and differential growth rates between sequential vertebrae and vertebral regions. Specifically, relative differences in the length of vertebrae indicate increasing differences caudad. Vertebral length in neonates increases from the atlas to the middle of the thoracic series and decreases in length caudad, while adult vertebral lengths tend to increase caudad. There is also a general trend of increasing vertebral and regional initial growth and rate of growth decay caudad. Anteroposterior patterns of growth are sexually dimorphic, with males having longer vertebrae than females at any given age. Differences are more pronounced (a) increasingly caudad along the body axis, and (b) in adulthood than in neonates. Elucidated patterns of growth are influenced by a combination of developmental, functional, and genetic factors.     

Effect of loading rate on endplate and vertebral body strength in human lumbar vertebrae

Previous studies have implied that increases in loading rate resulted in changes in vertebral mechanical properties and these changes were causative factors in the different fracture types seen with high-speed events. Thus many researchers have explored the vertebral body response under various loading rate conditions. No other study has investigated the role of the endplate in high-speed vertebral injuries. The current study determined changes in the endplate and vertebral body strength with increases in displacement rate. The endplate and vertebral body failure loads in individual lumbar vertebrae were documented for two displacement rates: 10 and 2500 mm/s. Using cross-sectional areas from the endplate and vertebral body, failure stresses for both components were calculated and compared. Both the endplate and vertebral body failure loads increased significantly with increased loading rate (p<0.005). Although the vertebral body failure stress increased significantly with loading rate as well (p<0.01), the endplate stresses did not (p>0.35). In addition, the endplate and vertebral strengths were not significantly different under high-speed loading (p>0.60), which inhibits possible predictions as to which bony component would fail initially during a high-speed injury event. It is possible that load distribution may contribute more to the fracture patterns seen at high speeds over vertebral component strength.     

Morphology,Morphogenesis and Small Subunit rRNA Gene Sequence of a Soil Hypotrichous Ciliate,Perisincirra paucicirrata (Ciliophora,Kahliellidae), from the Shoreline of the Yellow River,North China

The morphology, morphogenesis, and 18S rRNA gene sequence of a soil hypotrichous ciliate Perisincirra paucicirrata, isolated from north China, were investigated. Perisincirra paucicirrata differs from its congeners in: (1) having a body length to width ratio in vivo of 4:1, (2) its adoral zone occupying between 15% and 25% of the total body length, and (3) the presence of two parabuccal cirri, three left (with 10–16 cirri each) and two right marginal rows (with 14–24 cirri each), and three dorsal kineties. Our study offers a first attempt to begin to map the morphogenetic processes of the genus, which are mainly characterised by the following: the formation of four frontal ventral transverse anlagens for each daughter cell, with the proter's anlage I originating from the reorganised anterior part of the parental paroral; the paroral and endoral anlage developed from the reorganised old endoral and do not contribute the first frontal cirrus; the frontoventral transverse anlage I contributing the left frontal cirrus; anlage II generating the middle frontal and the buccal cirri; anlage III developing the right frontal cirrus and the anterior parabuccal cirrus; and anlage IV contributing the posterior parabuccal cirrus. As an additional contribution, we judge that the inner one or the two right rows of P. kahli and P. longicirrata are marginal rows. Phylogenetic analysis based on SSU rDNA sequences suggests that Perisincirra is related to sporadotrichids, but provides no credible evidence for its taxonomic position.     

From lizard body form to serpentiform morphology: The atlas–axis complex in African cordyliformes and their relatives

The comparative vertebral morphology of the atlas–axis complex in cordyliforms, xantusiid and several skinks is studied here. These lizards are particularly interesting because of their different ecological adaptations and anti‐predation strategies, where conformation ranges from the lizard‐like body to a snake‐like body. This transition to serpentiform morphology shows several evolutionary patterns in the atlas–axis complex: 1) the zygapophyseal articulations are lost in the early stage of the transition. In contrast to mammals, the atlas is more or less locked to the axis in lepidosaurs, but the absence of zygapophyseal articulation releases this locking for rotation. However despite its serpentiform morphology, Chamaesaura is different, in possessing this articulation; 2) the first intercentrum of Chamaesaura and Tetradactylus africanus (serpentiform grass‐swimmers) is fully curved anteriorly, underlying the occipital condyle. While this limits ventral skull rotation beyond a certain angle, it locks the skull, which is a crucial adaptation for a sit‐and‐wait position in grassland habitats that needs to keep the head stabilized; and 3) in Acontias, most of the atlas articular surface with the occipital condyle is formed by the lateral aspect of the articulation area relative to the area located in the dorsal region of the slightly reduced intercentrum. A similar state occurs in amphisbaenians, most likely reflecting a fossorial lifestyle of the limbless lizards. Although Chamaesaura and Tetradactylus live sympatrically in grasslands, Chamaesaura differs in several ways in atlas–axis complex: for example, aforementioned presence of the atlas–axis zygapophyseal articulation, and long posterodorsal processes. Its occipital condyle protrudes further posteriorly, placing the atlas–axis complex further from the endocranium than in Tetradactylus. Hence, adaptation in the same niche, even among sister clades, can lead to different atlas–axis morphology due to different lifestyle strategies, for example, different foraging mode, while similar atlas–axis morphology can evolve in two lineages occupying different niches, as in Ablepharus and Scelotes. J. Morphol. 277:512–536, 2016. © 2016 Wiley Periodicals, Inc.     

Development of the turtle carapace: Implications for the evolution of a novel bauplan

The chelonian carapace is composed of the endochondral ribs and vertebrae associated with a specialized dermis. The ribs are found in an aberrant position compared to those of all other tetrapods; they are superficial and dorsal to the limb girdles. This morphological arrangement, which constitutes the unique chelonian Bauplan, is examined from a developmental perspective. Embryos of Chelydra serpentina were studied during stages of carapace development. Tissue morphology, autoradiography, and indirect immunofluorescent localization of adhesion molecules indicate that the outgrowth of the embryonic carapace occurs as the result of an epithelial–mesenchymal interaction in the body wall. A carapacial ridge composed of mesenchyme of the dermis and overlying ectoderm is formed dorsal to the ectodermal boundary between somitic and lateral plate mesoderm. It is the anlage of the carapace margin, in which the ribs will eventually terminate. The ectoderm of the carapacial ridge is thickened into a pseudostratified columnar epithelium, which overlies a condensation in the mesenchyme of the dermis. Patterns of cell proliferation and the distribution of N-CAM and fibronectin in the carapacial ridge are consistent with patterns seen in other structures initiated by epithelial–mesenchymal interactions such as feathers and limb buds. Based on an analogy to this developmental mechanism in the development of the limb skeleton, a further analogy with the evolution of the limbs from lateral fin folds is used to form a hypothesis on the evolution of the carapace from elements of the primitive reptilian integument.     

Regeneration of the skeleton by recombinant human bone morphogenetic proteins

Recombinant human bone morphogenetic proteins (rhBMPs) have past a long journey in human orthopaedic surgery during the last 15 years. From the first reports of the use of rhBMPs in hostile environments such as critically-sized bone defects, avascular femoral head necrosis, unstable thoracolumbar vertebral fractures, instability between the atlas and axis due to rheumatoid arthritis; over the use for nonunions of long bones and the scaphoid, reconstructive and revision surgeries of the hip, acute fractures, allograft nonunions, congenital pseudarthrosis, and various approaches of lumbar and cervical spine fusions, rhBMPs overgrow to a safe and reliable device in the treatment of open tibial shaft fractures, nonunions of long bone fractures, anterior lumbar interbody fusion and revision posterolateral lumbar fusions. Systematic review of the published literature of rhBMPs is presented.     

Foxn1 is essential for vascularization of the murine thymus anlage

We addressed whether vascularization of the thymus anlage depends on Foxn1 expression. In the thymus anlagen of wild-type mice, CD31⁺ endothelial cells are initially observed between epithelial cells on embryonic day (Ed)12.5 and form luminal structure on Ed13. VEGF are produced in epithelial cells and mesenchymal cells which invaginate in the epithelial region of the anlagen on Ed13. However, in the nude thymus anlagen, neither CD31⁺ cells nor VEGF producing mesenchymal cells is detected in the epithelial region. The present results indicate that Foxn1 dependent epithelial development is essential for vascularization of the thymus anlagen.     

BMP signaling is required for normal thymus development

The microenvironment of the thymus fosters the generation of a diverse and self-tolerant T cell repertoire from a pool of essentially random specificities. Epithelial as well as mesenchymal cells contribute to the thymic stroma, but little is known about the factors that allow for communication between the two cells types that shape the thymic microenvironment. In this study, we investigated the role of bone morphogenetic protein (BMP) signaling in thymus development. Transgenic expression of the BMP antagonist Noggin in thymic epithelial cells under the control of a Foxn1 promoter in the mouse leads to dysplastic thymic lobes of drastically reduced size that are ectopically located in the neck at the level of the hyoid bone. Interestingly, the small number of thymocytes in these thymic lobes develops with normal kinetics and shows a wild-type phenotype. Organ initiation of the embryonic thymic anlage in these Noggin transgenic mice occurs as in wild-type mice, but the tight temporal and spatial regulation of BMP4 expression is abrogated in subsequent differentiation stages. We show that transgenic Noggin blocks BMP signaling in epithelial as well as mesenchymal cells of the thymic anlage. Our data demonstrate that BMP signaling is crucial for thymus development and that it is the thymic stroma rather than developing thymocytes that depends on BMP signals.     

Ultrastructural characteristics of the microcirculatory bed of the human adrenal cortex in prenatal ontogenesis

By means of transmissive electron microscopy the adrenals have been studied in 25 human embryos and fetuses at the age of 6-36 weeks. Certain stages have been revealed in formation of the adrenal cortex microcirculatory bed. In 6-7-week-old embryos (period of diffuse protocapillary bed) endothelial structure and mesenchymal cells, surrounding the adrenal anlage, resemble one another. A distinguished feature of the endothelium is regularly revealed desmosomes and large vacuoles, often found in cytoplasm of endotheliocytes. In 8-12-week-old fetuses (period when the organospecific microcirculatory bed is forming) sinusoid capillaries differentiate in the internal zone of the adrenal cortex; in endothelium fenestrae, "hatches", "locks" are revealed, the capillary basal membrane is formed. During subsequent time of the intrauterine development perfection of the microcirculatory pathways in the adrenals takes place, the arteriolar link of the subcapsular layer including. By the time of birth morphofunctional maturity of the microcirculatory bed in the adrenal cortex is noted.     

Functional morphology and anatomy of cervical vertebrae in Nacholapithecus kerioi, a middle Miocene hominoid from Kenya

This paper describes the morphology of cervical vertebrae in Nacholapithecus kerioi, a middle Miocene primate species excavated from Nachola, Kenya in 1999-2002. The cervical vertebrae in Nacholapithecus are larger than those of Papio cynocephalus. They are more robust relative to more caudal vertebral bones. Since Nacholapithecus had large forelimbs, it is assumed that strong cervical vertebrae would have been required to resist muscle reaction forces during locomotion. On the other hand, the vertebral foramen of the lower cervical vertebrae in Nacholapithecus is almost the same size as or smaller than that of P. cynocephalus. Atlas specimens of Nacholapithecus resemble those of extant great apes with regard to the superior articular facet, and they have an anterior tubercle trait intermediate between that of extant apes and other primate species. Nacholapithecus has a relatively short and thick dens on the axis, similar to those of extant great apes and the axis body shape is intermediate between that of extant apes and other primates. Moreover, an intermediate trait between extant great apes and other primate species has been indicated with regard to the angle between the prezygapophyseal articular facets of the axis in Nacholapithecus. Although the atlas of Nacholapithecus is inferred as having a primitive morphology (i.e., possessing a lateral bridge), the shape of the atlas and axis leads to speculation that locomotion or posture in Nacholapithecus involved more orthograde behavior similar to that of extant apes, and, in so far as cervical vertebral morphology is concerned, it is thought that Nacholapithecus was incipiently specialized toward the characteristics of extant hominoids.