Septal Ridges Research Articles

Identification of a myofibroblast differentiation program during neonatal lung development.

Alveologenesis is the final stage of lung development in which the internal surface area of the lung is increased to facilitate efficient gas exchange in the mature organism. The first phase of alveologenesis involves the formation of septal ridges (secondary septae) and the second phase involves thinning of the alveolar septa. Within secondary septa, mesenchymal cells include a transient population of alveolar myofibroblasts (MyoFBs) and a stable but poorly described population of lipid-rich cells that have been referred to as lipofibroblasts or matrix fibroblasts (MatFBs). Using a unique Fgf18CreER lineage trace mouse line, cell sorting, single-cell RNA sequencing and primary cell culture, we have identified multiple subtypes of mesenchymal cells in the neonatal lung, including an immature progenitor cell that gives rise to mature MyoFB. We also show that the endogenous and targeted ROSA26 locus serves as a sensitive reporter for MyoFB maturation. These studies identify a MyoFB differentiation program that is distinct from other mesenchymal cell types and increases the known repertoire of mesenchymal cell types in the neonatal lung.

Development of the terminal air spaces in the gray short-tailed opossum (Monodelphis domestica)- 3D reconstruction by microcomputed tomography.

Marsupials are born with structurally immature lungs when compared to eutherian mammals. The gray short-tailed opossum (Monodelphis domestica) is born at the late canalicular stage of lung development. Despite the high degree of immaturity, the lung is functioning as respiratory organ, however supported by the skin for gas exchange during the first postnatal days. Consequently, the majority of lung development takes place in ventilated functioning state during the postnatal period. Microcomputed tomography (μCT) was used to three-dimensionally reconstruct the terminal air spaces in order to reveal the timeline of lung morphogenesis. In addition, lung and air space volume as well as surface area were determined to assess the functional relevance of the structural changes in the developing lung. The development of the terminal air spaces was examined in 35 animals from embryonic day 13, during the postnatal period (neonate to 57 days) and in adults. At birth, the lung of Monodelphis domestica consists of few large terminal air spaces, which are poorly subdivided and open directly from short lobar bronchioles. During the first postnatal week the number of smaller terminal air spaces increases and numerous septal ridges indicate a process of subdivision, attaining the saccular stage by 7 postnatal days. The 3D reconstructions of the terminal air spaces demonstrated massive increases in air sac number and architectural complexity during the postnatal period. Between 28 and 35 postnatal days alveolarization started. Respiratory bronchioles, alveolar ducts and a typical acinus developed. The volume of the air spaces and the surface area for gas exchange increased markedly with alveolarization. The structural transformation from large terminal sacs to the final alveolar lung in the gray short-tailed opossum follows similar patterns as described in other marsupial and placental mammals. The processes involved in sacculation and alveolarization during lung development seem to be highly conservative within mammalian evolution.

A new discoid heliolitid (Proporidae) from the Upper Ordovician of the Baltic area: Morphology and modalities of increase

A species of Proporidae (Heliolitida) forming very small, discoid coralla, is fully described. It is mainly preserved in natural moulds in the Öjlemyr chert, an erratic silicified limestone found in Eridanos deposits surfacing in the west and north-east of the Dutch Overijssel-province and adjoining German area, generally accepted to be Uppermost Katian. The material is assigned to the rehabilitated Pinacopora Nicholson & Etheridge, 1878, a genus closely allied to Propora Milne-Edwards & Haime, 1849, and a new species, Pinacopora baltica is named. The main feature of this species, besides the characteristics of the genus and the biometric data, is the presence of wide, short, and convex septal ridges bearing scattered septal spines, alternating with narrow interseptal furrows. For the first time in heliolitids a pleurodictyoid pattern of growth is described. Only two species of Pinacopora are recorded: P. baltica n. sp. (Upper Ordovician) and P. grayi Nicholson & Etheridge, 1878 (Lower Silurian), respectively from Baltica and Laurentia.

Morphological Study of Fossa Ovalis in Formalin-Fixed Human Hearts and Its Clinical Importance.

Background and Objectives: Our study aimed to investigate the gross anatomy aspects of the fossa ovalis (FO) and the presence of some anatomical variation resulting from the incomplete fusion of septum primum and septum secundum, such as an atrial septal pouch (SP) and left atrial septal ridge. Materials and Methods: Thirty-one adult human hearts removed from formalin-fixed specimens were examined to provide information about the morphology of the FO. The organs were free of any gross anatomically visible pathological conditions. Results: The most common variants were the FO located in the inferior part of the interatrial septum (64.51%), circular (61.3%), with a net-like structure (51.62%), prominent limbus (93.55%), and patent foramen ovale (PFO) (25.8%). The right SP was observed in 9.67% of specimens, the left SP was observed in 29.03% of cases, and in 51.61% of cases, a double SP was observed. One sample presented a right SP and a double left SP, and one case showed a triple left SP, which was not reported previously to our knowledge. Conclusions: Knowledge of the interatrial septal anatomy becomes important for interventional cardiologists and should be documented before transeptal puncture.

Early postnatal lung development in the eastern quoll (Dasyurus viverrinus)

AbstractEarly postnatal lung development (1–25 days) in the eastern quoll (Dasyurus viverrinus) was investigated to assess the morphofunctional status of one of the most immature marsupial neonates. Lung volume, surface density, surface area, and parenchymal and nonparenchymal volume proportions were determined using light microscopic morphometry. The lungs of the neonate were at the canalicular stage and consisted of two “balloon‐like” airways with few septal ridges. The absolute volume of the lung was only 0.0009 cm3 with an air space surface density of 108.83 cm−1 and a surface area of 0.082 cm2. The increase in lung volume in the first three postnatal days was mainly due to airspace expansion. The rapid postnatal development of the lung was indicated by an increase in the septal proportion of the parenchyma around day 4, which was reflected by an increase in the airspace surface density and surface area. By day 5, the lung entered the saccular stage of development with a reduction in septal thickness, expansion of the tubules into saccules and development of a double capillary system. The subsequent saccular period was characterized by repetitive septation steps, which increased the number of airway generations. The lungs of the newborn Dasyurus viverrinus must be considered as structurally and quantitatively insufficient to meet the respiratory requirements at birth. Hence, cutaneous gas exchange might be crucial for the first three postnatal days. The lung has to mature rapidly in the early postnatal period to support the increased metabolic requirements of the developing young.

Identification of a FGF18-expressing alveolar myofibroblast that is developmentally cleared during alveologenesis.

Alveologenesis is an essential developmental process that increases the surface area of the lung through the formation of septal ridges. In the mouse, septation occurs postnatally and is thought to require the alveolar myofibroblast (AMF). Though abundant during alveologenesis, markers for AMFs are minimally detected in the adult. After septation, the alveolar walls thin to allow efficient gas exchange. Both loss of AMFs or retention and differentiation into another cell type during septal thinning have been proposed. Using a novel Fgf18:CreERT2 allele to lineage trace AMFs, we demonstrate that most AMFs are developmentally cleared during alveologenesis. Lung mesenchyme also contains other poorly described cell types, including alveolar lipofibroblasts (ALF). We show that Gli1:CreERT2 marks both AMFs as well as ALFs, and lineage tracing shows that ALFs are retained in adult alveoli while AMFs are lost. We further show that multiple immune cell populations contain lineage-labeled particles, suggesting a phagocytic role in the clearance of AMFs. The demonstration that the AMF lineage is depleted during septal thinning through a phagocytic process provides a mechanism for the clearance of a transient developmental cell population.

Morphological variations of the interatrial septum in ovine heart.

Smooth septum interatrial septum, patent foramen ovale (PFO) channel and atrial septal pouches (SPs) are commonly described variants in humans. Recent discoveries on the clinical significance of left-sided SP may encourage the creation of new strategies and devices for the management of SPs. However, these strategies may first be tested in the ovine model before implementation in humans. Unfortunately, little is known about the presence of SPs in ovine. In this study a total of 60 ovine (Ovis aries) hearts were examined. The interatrial septum morphology was assessed and the PFO channel and SPs were measured. The most commonly occurring variant were PFO channels (25.0%) with channel lengths of 5.4±2.3 mm. Smooth septums were observed in 18.3% of hearts. In the remaining cases, septums had a left septal ridge (15.0%), left SP (11.7%), left septal bridge (10.0%), right SP (10.0%), or had both a right SP and left septal ridge (10.0%). No double SPs were observed. The mean right SP depth was 3.4 ± 1.2 mm, and its mean ostium width and height were 7.9±1.8 mm and 2.8±1.0, respectively. For the left SP, the mean depth was 6.0±1.7mm, the ostium width was 7.9±2.4mm, and the ostium height was 4.1±1.6mm (range: 2.3–6.4mm). In conclusion the interatrial septum of ovine hearts exhibit morphologies that are more similar to humans than they are to swine, which should be taken into account during experimental studies. The presence of a left SP in sheep hearts make ovine models a promising alternative to the human heart for developing left-sided SP management devices and techniques.

Porcine heart interatrial septum anatomy

BackgroundThe left-sided atrial septal pouch (SP), a recently re-discovered anatomical structure within the human interatrial septum, has emerged as a possible source of thrombi formation and a trigger for atrial fibrillation, thereby potentially increasing the risk for ischemic stroke. In many studies, the swine interatrial septum has been used as model of the human heart. Also, possible new strategies and devices for management of the SPs may first be tested in this pig model. Therefore, in this study, we aimed to evaluate swine interatrial septum morphology and to compare it with the human analog, especially in the light of SP occurrence. MethodsA total of 75 swine (Sus scrofa f. domestica) hearts were examined. The interatrial septum morphology was assessed, and SPs were measured. ResultsThe most common variant of the interatrial septum was smooth septum (26.6%) followed by the patent foramen ovale channel and right SP (both 22.7%). No left or double SPs were observed. In 28.0% of all cases the fold of tissue (left septal ridge) was observed on the left side of the interatrial septum in the location where the left-sided SP should be expected. The mean length of the patent foramen ovale channel was 7.1±1.5mm. The mean right SP depth was 6.3±2.2mm, and its ostium width and height were 5.8±1.2 and 5.3±1.6mm, respectively. ConclusionsThere are significant differences between human and porcine interatrial septum morphology that should be taken into account during experimental studies. The absence of the left SP in swine results in the inability to use porcine heart as an experimental model for left-sided SP management.

A three-dimensional study of alveologenesis in mouse lung

Alveologenesis is the final step of lung maturation, which subdivides the alveolar region of the lung into smaller units called alveoli. Each of the nascent dividers serves as a new gas-exchange surface, and collectively they drastically increase the surface area for breathing. Disruption of alveologenesis results in simplification of alveoli, as is seen in premature infants diagnosed with bronchopulmonary dysplasia (BPD), a prevalent lung disease that is often associated with lifelong breathing deficiencies. To date, a majority of studies of alveologenesis rely on two-dimensional (2D) analysis of tissue sections. Given that an overarching theme of alveologenesis is thinning and extension of the epithelium and mesenchyme to facilitate gas exchange, often only a small portion of a cell or a cellular structure is represented in a single 2D plane. Here, we use a three-dimensional (3D) approach to examine the structural architecture and cellular composition of myofibroblasts, alveolar type 2 cells, elastin and lipid droplets in normal as well as BPD-like mouse lung. We found that 2D finger-like septal crests, commonly used to depict growing alveolar septae, are often artifacts of sectioning through fully established alveolar walls. Instead, a more accurate representation of growing septae are 3D ridges that are lined by platelet-derived growth factor receptor alpha (PDGFRA) and alpha smooth muscle actin (α-SMA)-expressing myofibroblasts, as well as the elastin fibers that they produce. Accordingly in 3D, both α-SMA and elastin were each found in connected networks underlying the 3D septal ridges rather than as isolated dots at the tip of 2D septal crests. Analysis through representative stages of alveologenesis revealed unappreciated dynamic changes in these patterns. PDGFRA-expressing cells are only α-SMA-positive during the first phase of alveologenesis, but not in the second phase, suggesting that the two phases of septae formation may be driven by distinct mechanisms. Thin elastin fibers are already present in the alveolar region prior to alveologenesis, suggesting that during alveologenesis, there is not only new elastin deposition, but also extensive remodeling to transform thin and uniformly distributed fibers into thick cables that rim the nascent septae. Analysis of several genetic as well as hyperoxia-induced models of BPD revealed that the myofibroblast organization is perturbed in all, regardless of whether the origin of defect is epithelial, mesenchymal, endothelial or environmental. Finally, analysis of relative position of PDGFRA-positive cells and alveolar type 2 cells reveal that during alveologenesis, these two cell types are not always adjacent to one another. This result suggests that the niche and progenitor relationship afforded by their close juxtaposition in the adult lung may be a later acquired property. These insights revealed by 3D reconstruction of the septae set the foundation for future investigations of the mechanisms driving normal alveologenesis, as well as causes of alveolar simplification in BPD.

Frasnian rugose and tabulate corals from the eastern Taurus (Kozan region, Turkey)

A section near the Kilgen Lake (Adana Province) has yielded a fauna of rugose and tabulate corals including Disphyllum cf. rugosum (Wedekind, 1922), D. cf. curtum Hill, 1954, Wapitiphyllum sp., Thamnopora sp., and Alveolites sp. This coral assemblage is consistent with the previous Frasnian age assigned to the limestones of the Gümüşali Formation. The rather well-preserved material provides new data on the structure and microstructure of Disphyllum and allows to describe in Thamnopora unusual calicinal morphology (septal ridges, median teeth, and pseudopercula) as well as new structures linked to the lateral increase (basal low wall, apical cul-de-sac).

Prominent Septal Hypertrophy: A Contra-Indication for Transapical Aortic Valve Implantation?

We report a case of transapical aortic valve implantation in a patient with severe left ventricular hypertrophy. The valve was deployed but failed to attain stable seating because of a hypertrophied septal ridge encroaching on the landing zone. Moderate perivalvar insufficiency was also noted. A second valve was deployed in an attempt to achieve stable seating and correct the perivalvar leak. This was unsuccessful and the two-valve complex embolized into the ascending aorta. The valves were moved and seated in the proximal descending thoracic aorta. The technical issues of transapical aortic valve implantation in patients with severe left ventricular hypertrophy are reviewed.

284 Establishment and characterization of individualized patient-derived low passage human tumor models: Development, validation and evaluation for clinical correlation analysis

Alveologenesis is the final step of lung maturation, which subdivides the alveolar region of the lung into smaller units called alveoli. Each of the nascent dividers serves as a new gas-exchange surface, and collectively they drastically increase the surface area for breathing. Disruption of alveologenesis results in simplification of alveoli, as is seen in premature infants diagnosed with bronchopulmonary dysplasia (BPD), a prevalent lung disease that is often associated with lifelong breathing deficiencies. To date, a majority of studies of alveologenesis rely on two-dimensional (2D) analysis of tissue sections. Given that an overarching theme of alveologenesis is thinning and extension of the epithelium and mesenchyme to facilitate gas exchange, often only a small portion of a cell or a cellular structure is represented in a single 2D plane. Here, we use a three-dimensional (3D) approach to examine the structural architecture and cellular composition of myofibroblasts, alveolar type 2 cells, elastin and lipid droplets in normal as well as BPD-like mouse lung. We found that 2D finger-like septal crests, commonly used to depict growing alveolar septae, are often artifacts of sectioning through fully established alveolar walls. Instead, a more accurate representation of growing septae are 3D ridges that are lined by platelet-derived growth factor receptor alpha (PDGFRA) and alpha smooth muscle actin (α-SMA)-expressing myofibroblasts, as well as the elastin fibers that they produce. Accordingly in 3D, both α-SMA and elastin were each found in connected networks underlying the 3D septal ridges rather than as isolated dots at the tip of 2D septal crests. Analysis through representative stages of alveologenesis revealed unappreciated dynamic changes in these patterns. PDGFRA-expressing cells are only α-SMA-positive during the first phase of alveologenesis, but not in the second phase, suggesting that the two phases of septae formation may be driven by distinct mechanisms. Thin elastin fibers are already present in the alveolar region prior to alveologenesis, suggesting that during alveologenesis, there is not only new elastin deposition, but also extensive remodeling to transform thin and uniformly distributed fibers into thick cables that rim the nascent septae. Analysis of several genetic as well as hyperoxia-induced models of BPD revealed that the myofibroblast organization is perturbed in all, regardless of whether the origin of defect is epithelial, mesenchymal, endothelial or environmental. Finally, analysis of relative position of PDGFRA-positive cells and alveolar type 2 cells reveal that during alveologenesis, these two cell types are not always adjacent to one another. This result suggests that the niche and progenitor relationship afforded by their close juxtaposition in the adult lung may be a later acquired property. These insights revealed by 3D reconstruction of the septae set the foundation for future investigations of the mechanisms driving normal alveologenesis, as well as causes of alveolar simplification in BPD.

Tracheal Hypoplasia with a Discrete Subaortic Septal Ridge in a Rottweiler Puppy

Concurrent tracheal hypoplasia and discrete subaortic stenosis are described in a 12-week-old Rottweiler puppy that presumably died of pulmonary edema. A brief literature review and comparison to previously published cases of tracheal hypoplasia in other breeds is presented along with a description of a subaortic septal ridge and comparison to the analogous condition in humans.

Multiple accessory left atrial appendages along a semi-circular path

A 51-year-old man with suspected coronary artery disease was referred for coronary computed tomographic (CT) angiography study by using a 64 detector-row multidetector CT scanner. There were no significant coronary stenoses. However, multiple accessory left atrial appendages (Panels A–D, arrowheads) were incidentally noted in the left atrium along a semicircular path, from anterior roof adjacent to the septal ridge (Panel C, arrow) …

Morphologic Characteristics of the Left Atrial Appendage, Roof, and Septum: Implications for the Ablation of Atrial Fibrillation

The left atrium (LA) ablation in different regions, including LA appendage (LAA), LA roof, and LA septum, has recently been proposed to improve the success rate of treating patients with atrial fibrillation (AF). The purpose of this study was to investigate the anatomy of LAA, LA roof, and LA septum, using computed tomography (CT). Multidetector CT scan was used to depict the LA in 47 patients with drug-refractory paroxysmal AF (39 males, age = 50 +/- 12 years) and 49 control subjects (34 males, age = 54 +/- 11 years). The area of LAA orifice, neck, and the length of roof line were greater in AF group than in control subjects. Three types of LAA locations and two types of LAA ridges were observed. Higher incidence of inferior LAA was noted in AF patients. The different morphologies of LA roof were described. Roof pouches were revealed in 15% of AF and 14% of controls. Moreover, we found septal ridge in 32% of AF and 23% of controls. Considerable variations of LAA and LA roof morphologies were demonstrated. Peculiar structures, including roof pouches and septal ridges, were delineated by CT imaging. These findings were important for determining the strategy of AF ablation and avoiding the procedure-related complications.

Powered Endoscopic Excision of the Septal Ridge

Powered Endoscopic Excision of the Septal Ridge

Die Laserchirurgie des mittleren Nasenganges bei der rezidivierenden Sinusitis*

We present our concept for treating patients suffering from recurrent sinusitis with coagulating lasers (Nd:YAG 1024 nm, Diode 810 or 904 nm). In these patients, the middle meatus is often narrowed by a hyperplastic middle turbinate, septum spurs and ridges, or by isolated polyps that block an ostium. We treat these patients by linear or punctate coagulation of the lateral wall of the middle turbinate, reducing the size of septum spurs, and blunting septal ridges or coagulating polyps. The outpatient procedure is performed with a laser fiberoptic system of 400 nm in contact mode with an energy of 3-5 watts. The amount of total energy applied to a specific tissue depends on the duration of laser contact at that point. The patient is anaesthesized superficially. Patients with a high degree of nasal hyperreactivity also receive antihistaminic preoperative treatment. Initial results show a significant increase of nasal flow with a decrease of sinus symptoms.

Distribution of fibronectin, type I collagen, type IV collagen, and laminin in the cardiac jelly of the mouse embryonic heart with retinoic acid-induced complete transposition of the great arteries.

In the mouse model of complete transposition of the great arteries (TGA) produced by all-trans retinoic acid (RA), parietal and septal ridges in the outflow tract (OT) are hypoplastic. At first, these ridges are generated by an expanded cardiac jelly (mainly myocardial basement membrane). Thereafter, endothelial cells delaminate and invade into the adjacent cardiac jelly to form endocardial cushion tissue (formation of cushion ridge). During cushion tissue formation, basement membrane antigens play an important role in the regulation of this endothelial-mesenchymal transformation. To examine whether the myocardial basement membrane components are altered in the RA-treated heart OT, immunohistochemistry for fibronectin, type I collagen, type IV collagen, and laminin was carried out in mouse embryonic hearts at 9.5 and 10.5 ED (embryonic day; vaginal plug = day 0) with or without prior exposure to RA. Particulate/fibrillar fibronectin and fibrillar type I collagen were observed in the thick cardiac jelly of the control heart at the onset of mesenchymal formation. In the RA-treated heart, an intermittent patchy staining for fibronectin and a sparse distribution of type I collagen were observed in the thin cardiac jelly. Laminin and type IV collagen were distributed continuously on the basal surface (layer adjacent to the basal plasma membrane) of endocardium and myocardium in both control and RA-treated hearts. The alterations in the antigens of the myocardial basement membrane (cardiac jelly) may be responsible for the hypoplasticity of parietal and septal ridges that characterizes RA-induced TGA morphology. This may be one of the reasons why mesenchymal cell formation is inhibited in the RA-induced TGA.

Ecophenotypic variation in the early Silurian rugose coral Palaeocyclus porpita

Summary Palaeocyclus porpita (Linnaeus) is a highly distinctive and biostratigraphically important early Silurian rugose coral, widespread in north-west Europe and with scattered records in North America. In eastern North America, Palaeocyclus rotuloides (Hall) occupies a similar biostratigraphical position, but differs from P. porpita in possessing a thin or imperfectly developed epitheca with septal ridges or exposed septal plates and a distinct profile to the undersurface. The calicular surfaces of P. rotuloides and P. porpita are essentially indistinguishable. The relationship between P. porpita and P. rotuloides is resolved by material from the Coralliferous Group of Dyfed, south-west Wales. Collections from siliciclastic horizons have P. porpita type epitheca, whereas material from thin bioclastic limestone beds has P. rotuloides type epitheca. P. rotuloides from eastern North America also appears to be associated with thin bioclastic limestones. It is suggested that these two forms were ecomorphs of the same species, P. porpita , in which epithecal development was influenced by the character of the substrate. The stratigraphical and palaeoecological distribution of the species is briefly reviewed.

Hypoplasia of cushion ridges in the proximal outflow tract elicits formation of a right ventricle-to-aortic route in retinoic acid-induced complete transposition of the great arteries in the mouse: scanning electron microscopic observations of corrosion cast models.

The major morphologic change associated with retinoic acid (RA)-induced complete transposition of the great arteries (TGA), a congenital malformation of the heart, was investigated in a mouse model in which TGA was found in 80% of surviving fetuses. Corrosion casts of embryonic hearts with or without prior exposure to retinoic acid were observed under a scanning electron microscope. In control hearts, indentations caused by expanded parietal and septal ridges in the outflow tract established right ventricle-to-left ventral pulmonic and left ventricle-to-right dorsal aortic routes before the aorticopulmonary septum completion. In RA-treated hearts, indentations of proximal regions of the parietal and septal ridges were small in the proximal outflow tract, whereas those in the distal regions developed well. These morphological features in the RA-treated hearts elicited right ventricle-to-right ventral aortic and left ventricle-to-left dorsal pulmonic routes in the TGA morphology. Hypoplasticity of the proximal regions of parietal and septal ridges in the outflow tract is one of the primary morphological abnormalities of the RA-induced TGA.