Anteroposterior Regions Research Articles

Extension of the Antero-Posterior Necrotic Regions Associated With Collapse Cessation in Osteonecrosis of the Femoral Head

BackgroundCollapse cessation is of utmost importance following a long period of collapse due to osteonecrosis of the femoral head (ONFH). This study investigated the relationship between collapse cessation and the extent of the necrotic regions of ONFH. MethodsOverall, 74 patients who had symptomatic ONFH (collapse < 3 mm) at the first visit with a minimum follow-up of 3 years were included in this study. Patients were categorized based on collapse progression or cessation into the progression and stable groups. The extent of the antero-posterior (AP) and medio-lateral necrotic regions between the groups was assessed using sagittal and coronal sections of T1-magnetic resonance imaging. Additionally, the most effective cutoff value was determined from the receiving operating characteristic curve where collapse cessation could be obtained, while the survival rates were determined with collapse progression as the endpoints were evaluated. ResultsOverall, 45 and 29 patients were in the progression and stable groups, respectively. The AP and medio-lateral necrotic regions were significantly different (P < .01 and P < .01, respectively) between the progression and stable groups. A cutoff value of 62.1% of the AP necrotic regions was determined from the receiving operating characteristic curve analysis. The 5-year survival rates with collapse progression as the endpoints were 5.4 and 77.8% in the AP necrotic regions of ≥62.1 and <62.1%, respectively (P < .01). ConclusionsCases with AP necrotic regions of ≤62.1% can be expected to have collapse cessation, which could be a useful index for ONFH treatment strategies. Level of EvidenceLevel IV.

Prosomeric Hypothalamic Distribution of Tyrosine Hydroxylase Positive Cells in Adolescent Rats.

Most of the studies on neurochemical mapping, connectivity, and physiology in the hypothalamic region were carried out in rats and under the columnar morphologic paradigm. According to the columnar model, the entire hypothalamic region lies ventrally within the diencephalon, which includes preoptic, anterior, tuberal, and mamillary anteroposterior regions, and sometimes identifying dorsal, intermediate, and ventral hypothalamic partitions. This model is weak in providing little or no experimentally corroborated causal explanation of such subdivisions. In contrast, the modern prosomeric model uses different axial assumptions based on the parallel courses of the brain floor, alar-basal boundary, and brain roof (all causally explained). This model also postulates that the hypothalamus and telencephalon jointly form the secondary prosencephalon, separately from and rostral to the diencephalon proper. The hypothalamus is divided into two neuromeric (transverse) parts called peduncular and terminal hypothalamus (PHy and THy). The classic anteroposterior (AP) divisions of the columnar hypothalamus are rather seen as dorsoventral subdivisions of the hypothalamic alar and basal plates. In this study, we offered a prosomeric immunohistochemical mapping in the rat of hypothalamic cells expressing tyrosine hydroxylase (TH), which is the enzyme that catalyzes the conversion of L-tyrosine to levodopa (L-DOPA) and a precursor of dopamine. This mapping was also combined with markers for diverse hypothalamic nuclei [agouti-related peptide (Agrp), arginine vasopressin (Avp), cocaine and amphetamine-regulated transcript (Cart), corticotropin releasing Hormone (Crh), melanin concentrating hormone (Mch), neuropeptide Y (Npy), oxytocin/neurophysin I (Oxt), proopiomelanocortin (Pomc), somatostatin (Sst), tyrosine hidroxilase (Th), and thyrotropin releasing hormone (Trh)]. TH-positive cells are particularly abundant within the periventricular stratum of the paraventricular and subparaventricular alar domains. In the tuberal region, most labeled cells are found in the acroterminal arcuate nucleus and in the terminal periventricular stratum. The dorsal retrotuberal region (PHy) contains the A13 cell group of TH-positive cells. In addition, some TH cells appear in the perimamillary and retromamillary regions. The prosomeric model proved useful for determining the precise location of TH-positive cells relative to possible origins of morphogenetic signals, thus aiding potential causal explanation of position-related specification of this hypothalamic cell type.

Hox gene expression predicts tetrapod-like axial regionalization in the skate, Leucoraja erinacea

The axial skeleton of tetrapods is organized into distinct anteroposterior regions of the vertebral column (cervical, trunk, sacral, and caudal), and transitions between these regions are determined by colinear anterior expression boundaries of Hox5/6, -9, -10, and -11 paralogy group genes within embryonic paraxial mesoderm. Fishes, conversely, exhibit little in the way of discrete axial regionalization, and this has led to scenarios of an origin of Hox-mediated axial skeletal complexity with the evolutionary transition to land in tetrapods. Here, combining geometric morphometric analysis of vertebral column morphology with cell lineage tracing of hox gene expression boundaries in developing embryos, we recover evidence of at least five distinct regions in the vertebral skeleton of a cartilaginous fish, the little skate (Leucoraja erinacea). We find that skate embryos exhibit tetrapod-like anteroposterior nesting of hox gene expression in their paraxial mesoderm, and we show that anterior expression boundaries of hox5/6, hox9, hox10, and hox11 paralogy group genes predict regional transitions in the differentiated skate axial skeleton. Our findings suggest that hox-based axial skeletal regionalization did not originate with tetrapods but rather has a much deeper evolutionary history than was previously appreciated.

Deconstructing the long-standing a priori assumption that serial homology generally involves ancestral similarity followed by anatomical divergence.

It has long been assumed that serial homologues are ancestrally similar-polysomerism resulting from a "duplication" or "repetition" of forms-and then often diverge-anisomerism, for example, as they become adapted to perform different tasks as is the case with the forelimb and hind limbs of humans. However, such an assumption, with crucial implications for comparative, evolutionary, and developmental biology, and for evolutionary developmental biology, has in general not really been tested by a broad analysis of the available empirical data. Perhaps not surprisingly, more recent anatomical comparisons, as well as molecular knowledge of how, for example, serial appendicular structures are patterned along with different anteroposterior regions of the body axis of bilateral animals, and how "homologous" patterning domains do not necessarily mark "homologous" morphological domains, are putting in question this paradigm. In fact, apart from showing that many so-called "serial homologues" might not be similar at all, recent works have shown that in at least some cases some "serial" structures are indeed more similar to each other in derived taxa than in phylogenetically more ancestral ones, as pointed out by authors such as Owen. In this article, we are taking a step back to question whether such assumptions are actually correct at all, in the first place. In particular, we review other cases of so-called "serial homologues" such as insect wings, arthropod walking appendages, Dipteran thoracic bristles, and the vertebrae, ribs, teeth, myomeres, feathers, and hairs of chordate animals. We show that: (a) there are almost never cases of true ancestral similarity; (b) in evolution, such structures-for example, vertebra-and/or their subparts-for example, "transverse processes"-many times display trends toward less similarity while in many others display trends toward more similarity, that is, one cannot say that there is a clear, overall trend to anisomerism.

Modal analysis of nanoindentation data, confirming that reduced bone turnover may cause increased tissue mineralization/elasticity.

It is widely believed that the activities of bone cells at the tissue scale not only govern the size of the vascular pore spaces (and hence, the amount of bone tissue available for actually carrying the loads), but also the characteristics of the extracellular bone matrix itself. In this context, increased mechanical stimulation (in mediolateral regions of human femora, as compared to anteroposterior regions) may lead to increased bone turnover, lower bone matrix mineralization, and therefore lower tissue modulus. On the other hand, resorption-only processes (in endosteal versus periosteal regions) may have the opposite effect. A modal analysis of nanoindentation data obtained on femurs from the Melbourne Femur Research Collection (MFRC) indeed confirms that bone is stiffer in endosteal regions compared to periosteal regions (E̅endost = 29.34 ± 0.75 GPa >E̅periost = 24.67 ± 1.63 GPa), most likely due to the aging-related increase in resorption modeling on endosteal surfaces resulting in trabecularization of cortical bone. The results also show that bone is stiffer along the anteroposterior direction compared the mediolateral direction (E̅anteropost = 28.89 ± 1.08 GPa >E̅mediolat = 26.03 ± 2.31 GPa), the former being aligned with the neutral bending axis of the femur and, thus, undergoing more resorption modeling and consequently being more mineralized.

Quantification of ventilation distribution in regional lung injury by electrical impedance tomography and xenon computed tomography

Validation studies of electrical impedance tomography (EIT) based assessment of regional ventilation under pathological conditions are required to prove that EIT can reliably quantify heterogeneous ventilation distribution with sufficient accuracy. The objective of our study was to validate EIT measurements of regional ventilation through a comparison with xenon-multidetector-row computed tomography (XeCT) in an animal model of sub-lobar lung injury. Nine anesthetized mechanically ventilated supine pigs were examined before and after the induction of lung injury in two adjacent sub-lobar segments of the right lung by saline lavage or endotoxin instillation. Regional ventilation was determined in 32 anteroposterior regions of interest in the right and left lungs and the ventilation change quantified by difference images between injury and control. Six animals were included in the final analysis. Measurements of regional ventilation by EIT and XeCT correlated well before (rs = 0.89 right, rs = 0.90 left lung) and after local injury (rs = 0.79 and 0.92, respectively). No bias and narrow limits of agreement were found during both conditions. The ventilation decrease in the right injured lung was correspondingly measured by both modalities (5.5%±1.1% by EIT and 5.4%±1.9% by XeCT, p = 0.94). EIT was inferior to clearly separate the exact anatomical location of the regional injuries. Regional ventilation was overestimated (<2%) in the most ventral and dorsal regions and underestimated (2%) in the middle regions by EIT compared to XeCT. This study shows that EIT is able to reliably discern even small ventilation changes on sub-lobar level.

Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates

Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates

Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

Role of the Onecut transcription factors in pancreas morphogenesis and in pancreatic and enteric endocrine differentiation

The Onecut (OC) transcription factor HNF-6 (OC-1) is required during embryogenesis for pancreatic specification, morphogenesis and endocrine differentiation. In mammals, HNF-6 has two paralogs, OC-2 and OC-3, which share DNA-binding and transcriptional activation properties and have expression patterns that overlap with that of HNF-6. This suggested that OC-2 and OC-3 play redundant roles with HNF-6 in pancreas development. Here, we have addressed this hypothesis by analyzing the phenotype of mice knockout for the Onecut factors. We found that neither OC-2 nor OC-3 is required for pancreas specification. However, OC-2 plays partially redundant roles with HNF-6 in pancreas morphogenesis and in the differentiation of endocrine precursors. As similar molecular events drive endocrine differentiation in the pancreas and gastrointestinal tract, we also investigated if Onecut factors are involved in enteroendocrine differentiation. OC-2 and OC-3 were found to delineate specific antero-posterior regions of the gut around embryonic day 12.5. Later on, OC2 was expressed in several gut cell types, whereas OC-3 behaved as a specific marker of the enteroendocrine lineage. However, OC-2 and OC-3, alone or in combination, were dispensable for gut development and enteroendocrine differentiation. In conclusion, our data reveal partially redundant roles for HNF-6 and OC-2 in developing pancreas and identify new markers for antero-posterior patterning of the gut and for enteroendocrine differentiation.

Paraxial mesoderm specifies zebrafish primary motoneuron subtype identity.

We provide the first analysis of how a segmentally reiterated pattern of neurons is specified along the anteroposterior axis of the vertebrate spinal cord by investigating how zebrafish primary motoneurons are patterned. Two identified primary motoneuron subtypes, MiP and CaP, occupy distinct locations within the ventral neural tube relative to overlying somites, express different genes and innervate different muscle territories. In all vertebrates examined so far, paraxial mesoderm-derived signals specify distinct motoneuron subpopulations in specific anteroposterior regions of the spinal cord. We show that signals from paraxial mesoderm also control the much finer-grained segmental patterning of zebrafish primary motoneurons. We examined primary motoneuron specification in several zebrafish mutants that have distinct effects on paraxial mesoderm development. Our findings suggest that in the absence of signals from paraxial mesoderm, primary motoneurons have a hybrid identity with respect to gene expression, and that under these conditions the CaP axon trajectory may be dominant.

EphA family gene expression in the developing mouse neocortex: regional patterns reveal intrinsic programs and extrinsic influence.

Parcellation of the mammalian cerebral cortex into distinct areas is essential for proper cortical function; however, the developmental program that results in the genesis of distinct areas is not fully understood. We examined the expression of members of the EphA family-the EphA receptor tyrosine kinases and the ephrin-A ligands-within the developing mouse cerebral cortex, with the aim of characterizing this component of the molecular landscape during cortical parcellation. We found that specific embryonic zones, such as the ventricular, subventricular, intermediate, subplate, and marginal zones, as well as the cortical plate, were positive for particular EphA genes early in corticogenesis (E12-E15). Along with this zone-selective expression, several genes (EphA3, EphA4, EphA5) were evenly expressed along the axes of the developing cortex, whereas one family member (EphA7) was expressed in a distinct anteroposterior pattern. Later in corticogenesis (E16-E18), other EphA family members became selectively expressed, but only within the cortical plate: EphA6 was present posteriorly, and ephrin-A5 was expressed within a middle region. At birth, patterning of EphA gene expression was striking. Thus, we found that the expression of a single EphA gene or a combination of family members can define distinct embryonic zones and anteroposterior regions of the neocortex during development. To examine whether cellular context affects the patterning of EphA expression, we examined gene expression in embryonic cortical cells grown in vitro, such that all cellular contacts are lacking, and in Mash-1 mutant mice, in which thalamocortical connections do not form. We found that the expression patterns of most EphA family members remained stable in these scenarios, whereas the pattern of ephrin-A5 was altered. Taken together, this work provides a comprehensive picture of EphA family expression during mouse corticogenesis and demonstrates that most EphA expression profiles are cell intrinsically based, whereas ephrin-A5 is plastically regulated.

Origins of anteroposterior patterning and Hox gene regulation during chordate evolution.

All chordates share a basic body plan and many common features of early development. Anteroposterior (AP) regions of the vertebrate neural tube are specified by a combinatorial pattern of Hox gene expression that is conserved in urochordates and cephalochordates. Another primitive feature of Hox gene regulation in all chordates is a sensitivity to retinoic acid during embryogenesis, and recent developmental genetic studies have demonstrated the essential role for retinoid signalling in vertebrates. Two AP regions develop within the chordate neural tube during gastrulation: an anterior 'forebrain-midbrain' region specified by Otx genes and a posterior 'hindbrain-spinal cord' region specified by Hox genes. A third, intermediate region corresponding to the midbrain or midbrain-hindbrain boundary develops at around the same time in vertebrates, and comparative data suggest that this was also present in the chordate ancestor. Within the anterior part of the Hox-expressing domain, however, vertebrates appear to have evolved unique roles for segmentation genes, such as Krox-20, in patterning the hindbrain. Genetic approaches in mammals and zebrafish, coupled with molecular phylogenetic studies in ascidians, amphioxus and lampreys, promise to reveal how the complex mechanisms that specify the vertebrate body plan may have arisen from a relatively simple set of ancestral developmental components.

Epithelial-mesenchymal signaling during the regionalization of the chick gut.

The development of the vertebrate gut requires signaling between the endoderm and mesoderm for establishing its normal anteroposterior (AP) axis and for tissue-specific differentiation. Factors implicated in positional specification of the AP regions of the gut include endodermally expressed Sonic hedgehog (Shh), mesodermally expressed Bmp4 and members of the Hox gene family. We have investigated the roles of these factors during AP regional specification of the chick embryonic gut. Early in gut development, the endoderm sends inductive signals to the mesoderm. Shh has been implicated as one of these signals. We find a differential response to exposure of the inductive influence of Shh along the AP axis of the gut. Virally mediated misexpression of Shh results in ectopic upregulation of its receptor Ptc and a cellular proliferation throughout the gut mesoderm. Although ectopic Shh can induce Bmp4 in the mesoderm of the midgut and hindgut, Bmp4 is not induced in the stomach region of the foregut. The stomach region has a thicker layer of mesoderm than the rest of the gut suggesting that the normal function of Bmp4 could be to limit mesodermal growth in the non-stomach regions of the gut. Ectopic Bmp4 expression in the stomach results in a reduction of the mesodermal component consistent with this hypothesis. In addition to the regional restriction on Bmp4 induction, Shh can only induce Hoxd-13 in the mesoderm of the hindgut. These findings suggest that a prepattern exists in the primitive gut mesoderm prior to expression of Shh in the endoderm. The gut mesoderm is subsequently responsible for inducing region-specific differentiation of its overlying endoderm. We tested the role of Hoxd-13, normally restricted in its mesodermal expression to the most posterior region of the hindgut (cloaca), in controlling adjacent endodermal differentiation. When virally mediated Hoxd-13 is misexpressed in the primitive midgut mesoderm, there is a transformation of the endoderm to the morphology and mucin content of the hindgut. Thus, the positionally restricted expression of a Hox gene in the gut mesoderm influences the inductive signaling that leads to regionally specific differentiation of gut endoderm.

Localization of types I, II and III collagen and glycosaminoglycans in the mandibular condyle of growing monkeys: an immunohistochemical study.

In order to analyse the regional and age-related variations of primate condyles, immunohistochemical techniques were used to examine the localization of types I, II and III collagen and a variety of glycosaminoglycans in distinct anteroposterior regions of the mandibular condyle of two growing female rhesus monkeys (Macaca mulatta). In the juvenile monkey staining for types I and III collagen was weak in the fibrous tissue layer, intense in the pre-cartilaginous tissue layer and faint in the cartilaginous tissue layer; staining was significantly more intense in the posterosuperior and posterior regions than in the anterior region. Similarly, staining for cartilage-characteristic extracellular matrices, including type II collagen and keratan sulfate, was intense in the cartilaginous tissue layer of the posterior condyle. In contrast, in the late-adolescent monkey staining for the extracellular matrices was more intense in the anterior half of the condyle (i.e. from the anterior to the posterosuperior region) than in the posterior region, and most intense in the posterosuperior region. The results demonstrate that marked regional differences exist in the phenotypic expression of the extracellular matrices in the mandibular condyles of growing monkeys and that these differences vary between different developmental stages. The variations probably reflect the predominance of competing growth and articulatory functions in the mandibular condyles.

Hensen's node regulates avian neural crest differentiation in vitro.

Different anteroposterior (AP) regions of the neural crest normally produce different cell types, both in vivo and in vitro. AP differences in neural crest cell fates appear to be specified in part by mechanisms that act prior to neural crest cell migration. We, therefore, examined the possibility that the fates of neural crest cells, like those of neural tube cells, can be regulated by interactions with Hensen's node. Using a transfilter co-culture system, we found that young (stage 3+ to 4) Hensen's node up-regulates the expression of two cranial-specific phenotypes (fibronectin and smooth muscle actin immunoreactivities) in mass cultures of trunk neural crest cells, and down-regulates the expression of a trunk-specific phenotype (melanin synthesis). The changes in phenotype produced by exposure to young Hensen's node were not accompanied by changes in the proliferation of either fibronectin immunoreactive cells or melanocytes. The capacity of Hensen's node to elicit changes in trunk neural crest cell phenotype decreased as the developmental age of the node increased and was lost by stage 6. In addition, old Hensen's node did not stimulate the expression of trunk-specific phenotypes in cranial neural crest cells, suggesting that cranial- and trunk-specific phenotypes are induced by different mechanisms.

Morphometric estimation of oxygen diffusing capacity for the air‐sac in the catfish Heteropneustes fossilis

A detailed morphometric study has been made of the air-sacs of this air-breathing catfish using whole mounts, light and electron microscopy, of six specimens, body weight 40±2 g. Measurements of surface areas of the gas exchange and non-respiratory surfaces have taken into account foldings of the surface at macro and ultramicroscopic levels. Area of the gas exchange surface was estimated as 23.915cm2 (=0.598cm2/g) which is 67%of the total surface area of the two air-sacs. Significant differences were found in some morphometric parameters which were related to the three antero-posterior regions into which air-sacs were divided. Harmonic mean thickness of the tissue component of the air/blood barrier was estimated for the whole air-sac as 0.342 μm. These and other measurements enabled the diffusing capacity for the air-sacs to be calculated as 0.0638 m1O2/min/mmHg/kg. These results show that Heteropneustes has an air-breathing organ which is superior to that of Amphipnous cuchia, similar to that of Lepidosiren, but less well developed than that of Protopterus. In addition, Heteropneustes is well adapted to obtain oxygen directly from water by means of its gills and skin as indicated by both morphometric and physiological measurements which also correlate with its life in ponds and streams which are Iiable to dry up.

Neuronal maturation in the normal and hypothyroid rat cerebellar cortex studied with monoclonal antibody MIT-23.

By immunocytochemistry we have studied the expression of the mitochondria-associated polypeptide MIT-23 during the postnatal development of the normal and hypothyroid rat cerebellar cortex, in afferent fibers, and also in neurons of the cerebellar nuclei. The glial cells are never immunoreactive. In all neurons of the cerebellar cortex, MIT-23 expression always occurs after the final mitosis and migration are complete, and persists throughout adult life. Almost all MIT-23 expression begins postnatally. A few Purkinje cells are already immunoreactive at birth and the rest begin expression during the following two days. Immunoreactive Golgi and granule cells are found from postnatal day 4 (P4), basket cells from P10, and stellate cells from P16. Purkinje cells from different anteroposterior regions of the vermis express different levels of MIT-23 with higher staining intensities in lobules I to IV. These differences appear early in development and are retained in the adult. MIT-23 expression in the hypothyroid cerebellar cortex differs from that in control animals only in minor ways. However, sections immunoperoxidase-stained with anti-MIT-23 antibody reveal that, in addition to previously reported alterations in cerebellar development due to a shortage of thyroid hormones, Purkinje cell axonal development is slowed down in the hypothyroid condition, and occasional Purkinje cells in normal and especially in hypothyroid animals have their somata and or dendrites in ectopic locations. Analysis of these cells reveals a preferential direction of dendritic trunk growth in the direction of the molecular layer. Furthermore, secondary branching of ectopic dendrites is confined exclusively to the developing molecular layer, as in normal Purkinje cells, thus suggesting that neither the mature nor immature granule cell environment is sufficient to sustain normal dendritic development.