Comparative kinematics of the vertebrate jaw frame.
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Antibody diversity in vertebrates arises through the coordinated actions of V(D)J recombination and somatic hypermutation (SHM). Cartilaginous fishes occupy a key phylogenetic position as the sister lineage to bony vertebrates and therefore provide important comparative insights into the evolution of adaptive immunity. This review focuses on the nurse shark (Ginglymostoma cirratum) as a representative model for examining antibody-diversification mechanisms in cartilaginous fishes. Shark immunoglobulin genes exhibit a multicluster organization, while immunoglobulin new antigen receptor (IgNAR), a heavy-chain-only isotype, contains a single variable domain with an extended complementarity-determining region 3 (CDR3) that can be stabilized by non-canonical disulfide bonds. These structural features, together with intracluster multi-D V(D)J recombination and distinctive SHM characterized by single and tandem substitutions and insertions/deletions, contribute to antibody diversification in sharks. By comparing cartilaginous fishes, ray-finned fishes, and mammals, this review highlights lineage-specific combinations of immunoglobulin gene organization, recombination, mutational processing, and affinity maturation. Within the heuristic framework proposed here, shark and mammalian systems are described as emphasizing "breadth-first" repertoire generation and "precision-first" affinity optimization, respectively. These terms indicate relative mechanistic emphases rather than mutually exclusive categories or sequential evolutionary stages, while ray-finned fishes exhibit a distinct combination of genomic organization and mutational features. Investigating antibody diversification in cartilaginous fishes not only advances our understanding of vertebrate immune evolution but also provides structural and mechanistic insights that may inform the development of engineered antibodies based on the IgNAR scaffold.
The expansion of the visual opsin gene family was a crucial event in the diversification of vertebrate vision in evolution. Additional expansions in phototransduction-related genes facilitated the development of dim-light (rods) and color vision (cones). Sequence-based phylogeny and gene positions from extant jawed vertebrate genomes are insufficient to untangle the visual opsin duplications in early vertebrates. Additionally, jawless vertebrates share a visual opsin gene repertoire with jawed vertebrates which conflicts with recent findings of distinct whole-genome duplications in each lineage. To resolve these questions, we analyzed jawless vertebrate genomes, focusing on visual opsin genes. Our findings, based on chromosomal arrangements and relationships, confirm tandem duplications of visual opsins before the vertebrate radiation.
As important members of the ETS superfamily, the E74-like factor (ELF) transcription factor family regulates gene transcription through a conserved ETS domain and plays critical roles in immune regulation. However, the evolutionary characteristics and functions of this family in lampreys (Lethenteron reissneri) remain unclear. In this study, the ELF gene family of lampreys (Lr-ELF1, Lr-ELF2, Lr-ELF3, and Lr-ELF5) was systematically identified, and their molecular evolutionary features and immune response functions were investigated. Phylogenetic analysis revealed evolutionary characteristics reflecting the transition from jawless to jawed vertebrates. Domain architecture, gene structure, and three-dimensional structural analyses indicated that these genes appear to be conserved among vertebrates, with their three-dimensional structures showing high similarity to the core secondary structural elements of human homologous proteins. Synteny analysis demonstrated significant differences in the genomic neighborhoods of ELF genes between lampreys and jawed vertebrates. Quantitative real-time PCR (qRT-PCR) was performed with three biological and three technical replicates; relative expression levels were calculated using the ΔCt method, and statistical analysis was carried out with GraphPad Prism 9. Quantitative real-time PCR (qRT-PCR) results suggested that the ELF gene family may be involved in immune defense. This study not only enriches our understanding of the evolution of ELF genes but also provides new insights into the roles of lamprey ELFs in immune defense.
Current knowledge of class-I cytokine receptors comes primarily from studies in jawed vertebrates (gnathostomes), and their origin and evolution remain unresolved. In this study, we identified a leptin receptor-like sequence (LepRL) and three interleukin-6 receptor subunit b-like sequences (IL6RBL) from a jawless vertebrate (cyclostome), the sea lamprey (Petromyzon marinus). Based on structural, phylogenetic, and syntenic analyses, we deduced that these lamprey receptors are likely distinct ohnologs to gnathostome LepR and IL6RB-related receptors, respectively, that arose in the two rounds of vertebrate whole-genome duplication (1R and 2R). Notably, lamprey LepRL likely originated from a different 1R progenitor than the one giving rise to gnathostome LepR during cyclostome hexaploidization. Differential patterns in mRNA expression of LepRL and IL6RBLs were observed among adult tissues, during larval metamorphosis, and in response to juvenile feeding. Feeding stimulated hepatic expression of LepRL and IL6RBL (namely, IL6RBL1) mRNAs in correlation with upregulation of insulin-like growth factor mRNA, whereas brain LepRL and IL6RBL1 mRNA expression was correlated positively with neuropeptide Y but inversely with intestinal content in fed juveniles. Notably, these observations along with immunolocalization of LepRL in the hypothalamus suggest a role of leptin signaling in regulating energy balance that is conserved among vertebrates. Additionally, seawater exposure stimulated branchial LepRL expression coincident with increased expression of ion transporters in ionocytes, indicating a role of leptin signaling in osmoregulation. These findings provide new insight into the early evolution of class-I cytokine receptors and reveal diverse functions of the leptin signaling system in jawless vertebrate.
The amino acid sequence of the alpha-chain of the major haemoglobin of a newt, T. granulosa, has been determined. The chain is 142 residues long and has an extra methionine at its N-terminus when compared with human alpha-chain. Most of the tryptic peptides were sequenced by a combination of the subtractive Edman method and by deduction from the compositions of overlapping fragments produced by various enzymic treatments. The sequence of two 'core' regions was obtained by automatic sequencing of large peptides produced by trypsin cleavage at arginine residues only after blockage of lysine residues by citraconylation; by cleavage between aspartic acid and proline residues with 70% formic acid, and by cyanogen bromide cleavage at methionine residues. The sequence of T. granulosa alpha-chain is compared with those of representative species from the other classes of vertebrates. The differences in alpha-chain between the classes of vertebrates are compared with the differences in this protein between an equal number of orders of mammals. This comparison allows us to conclude that the major functional and conformational features of alpha-chain have been conserved since the divergence of the classes of jawed vertebrates.
The tesserate pattern of endoskeletal calcification has been investigated in jaws, gill arches, vertebral arches and fins of the sharks Carcharhinus menisorrah, Triaenodon obesus and Negaprion brevirostris by techniques of light and electron microscopy. Individual tesserae develop peripherally at the boundary between cartilage and perichondrium. An inner zone, the body, is composed of calcified cartilage containing viable chondroxytes separated by basophilic contour lines which have been called Liesegang waves or rings. The outer zone of tesserae, the cap, is composed of calcified tissue which appears to be produced by perichondrial fibroblasts more directly, i.e., without first differentiating as chondroblasts. Furthermore, the cap zone is penetrated by acidophilic Sharpey fibers of collagen. It is suggested that scleroblasts of the cap zone could be classified as osteoblasts. If so, the cap could be considered a thin veneer of bone atop the calcified cartilage of the body of a tessera. By scanning electron microscopy it was observed that outer and inner surfaces of tesserae differ in appearance. Calcospherites and hydroxyapatite crystals similar to those commonly seen on the surface of bone are present on the outer surface of the tessera adjacent to the perichondrium. On the inner surface adjoining hyaline cartilage, however, calcospherites of variable size are the predominant surface feature. Transmission electron microscopy shows calcification in close association with coarse collagen fibrils on the outer side of a tessera, but such fibrils are absent from the cartilaginous matrix along the under side of tesserae. Calcified cartilage as a tissue type in the endoskeleton of sharks is a primitive vertebrate characteristic. Calcification in the tesserate pattern occurring in modern Chondrichthyes may be derived from an ancestral pattern of a continuous bed of calcified cartilage underlying a layer of perichondral bone, as theorized by Orvig ('51); or the tesserate pattern in these fish may itself be primitive.
Lateral cephalographs from 220 normal adolescent white orthodontic patients, and of individuals with craniofacial dysostosis and oculodento-osseous dysplasia were studied. Variations were observed in the morphology of the posterior margins of the superior articular processes, vertebral artery canals being present in 8%. Posterior arch dehiscence was found in eight individuals, including seven cases in the midline. Three patients had accessory ossicles above the posterior arch of the atlas, and two showed evidence of fusion of the second and third cervical vertebrae. The profile of the atlas was well outside the normal range in both syndromes studied.
Nine active neurohypophyseal principles have been isolated and identified among the vertebrates. Arginine-vasotocin is the most ubiquitous, occurring in pituitary glands from representatives of all the major vertebrate groups. There is much more variation in structure among the principles that resemble oxytocin. The manner in which these evolved remains unclear. Arginine-vasotocin stimulates smooth muscles from a wide variety of vertebrate species. It can stimulate contraction of oviducts from many jawed fishes and tetrapods. The oxytocin-like peptides are usually less active in this respect. Among adult mammals arginine-vasotocin is replaced by arginine-vasopressin which has much less oxytocin activity. Thus, although arginine-vasotocin may both stimulate oviducts and cause water retention in nonmammalian tetrapods, oxytocic and antidiuretic functions can be regulated independently by oxytocin and vasopressin in mammals. Arginine-vasotocin elicits vasoconstrictor responses in even the most primitive vertebrates. These may be systemic or regional. Their distribution may determine whether arginine-vasotocin acts as a diuretic or an antidiuretic agent. It is possible that the most primitive neurohypophyseal functions were related to cardiovascular regulation and that the neurohypophysis acquired its osmoregulatory functions later in vertebrate evolution.
Benign osteoblastoma is an uncommon, solitary, osteoid and bone-producing tumor which is characterized by prevalent active osteoblasts and rich vascularized delicate fibrous stroma, previously regarded as malignant. The term benign osteoblastoma was recently proposed by different authors to separate this lesion from other solitary benign bone tumors. It most often involves long bones and vertebral column and other bones, and also occurs in jaw bones. There is a close histopathologic similarity between benign osteoblastoma and osteoid osteoma; consequently, much debate about them exists. Benign osteoblastoma has a good prognosis and is best treated by curettage or conservative surgical excision. Recurrence is rare. Because of its rarity in jaw bones, one case of benign osteoblastoma of the mandible is reported.
Two cases of nevoid basal cell carcinoma syndrome were reported with a review of pertinent literature. The first case was a 59-year-old man, whose autopsy was warranted. Signs and symptoms manifested in this case were basal cell carcinoma, generalized multiple nevi, multiple cysts in the jaws and long bones, pits in the palm and sole, frontal and occipital bossing, ossification of the falx cerebri, a bifid rib, renal fibroma and a patent foramen ovale. The family history revealed a hereditary predisposition as to the syndrome. The patient in the second case included basal cell carcinoma, multiple nevi, multiple jaw cysts, pits in the palm and sole, frontal bossing, calcification of the falx cerebri, cervical vertebral fusion and high-arched palate.
Gaucher's disease is a rare metabolic disorder in which there is an abnormal accumulation of cerebrosides in the reticuloendothelial system due to a deficit of beta-glucuronidase. Three patients with this disease, 8, 14, and 23 years old, were studied. The purpose of this paper is to point out some of the roentgenologic findings, such as areas of femoral osteolysis, renal venous thrombosis, and in one patient, sclerosis of the sacroiliac joint. Splenomegaly and alteration of the tubular bony structure of the distal end of the femur were present in all three cases. The roentgenologic images of the disease are discussed. The osteoarticular system is the most often affected. Osteolysis is the basic lesion with expansion of the bone marrow and sclerosis. The earliest symptom and sometimes the only one is the Erlenmeyer flask deformity or widening of the distal portion of the femur. Sometimes there is a high degree of deossification without definite osteolytic lesions. Pathologic fractures and fractures caused by pressure of the vertebral bodies are common. Aseptic femoral necrosis are often present. Other less frequent sites of osteoarticular pathology are the skull, jaws, ribs, and sacroiliac joints. Splenomegaly is the most frequent visceral lesion. Other organs sometimes affected are the liver, kidneys, heart, lymphatic system, and lungs, with nodular or basal reticular infiltrations.
Previous studies on tooth replacement in lower vertebrates have been plagued by a lack of common integrative approaches and methods making it impossible to furnish a phylogenetic synthesis. This study is based on serial sections of the jaw of Prionurus microlepidotus. Each Toothgerm was characterized by its developmental stage and its position in the jaw. The relationship between the developmental stage of toothgerm and position in the jaw has been studied and expressed in several graphical illustrations. The following conclusions have been made: (1) The initiation of toothgerms in P. microlepidotus is governed by two Zahnreihen, which respectively initiate toothgerms on the lingual and labial side of the functioning teeth in an alternating pattern. (2) Therefore, functioning teeth in one locus are supplied by the alternate eruption of lingual and lubial toothgerms. (3) Advancing of tooth replacement in each locus is independent of functioning teeth and their successors in adjacent loci. (4) The disorders of replacement patterns are caused by an alternated rate of eruption of successive toothgerms as a response to unusual shedding of the functioning teeth.
The growth interrelation existing between the developing brain and its bony case (with the brain representing the morphogenetically determining structure to the shape and size of which the neurocranial bony envelope is adapted) is to be conceived just as a special case of a general phenomenon, the osteo-neural relation, which works throughout the entire vertebrate body. The morphological manifestations of this relation may be disclosed in the axial as well as in the appendicular skeleton. In the present communication the osteo-neural concept is applied to the morphogenesis of the facial skeleton with special reference to the mandible. The more or less elongated shape of the mandible in various species of vertebrates depends on the phylogenetically established higher or lesser degree of growth potentiality of the mandibular nerve. With the increasing size of the brain in the course of hominization the growth-in-length capability of the mandibular nerve is (compensatorily?) decreased with corresponding shortening of the mandible and with appearance of the chin. The proposed interpretation is supported by a model experiment. The highly characteristic shortening and angulation of the lower beak which may be produced experimentally in the chick embryo by a great variety of teratogens, is related most probably to the same underlying mechanism, viz., to the primary inhibition of the highly susceptible neural growth with the secondary adaptive deformity of the beak. Pierre-Robin-Syndrome (cleft palate and micrognathia) may be readily explained by a growth insufficiency of the palatine and mandibular nerves.
The oto-vertebral syndrome is a rare combination of malformations of the ears, spinal anomalies, and congenital heart disease. The syndrome appears to be caused by early embryonic exogenous damage during the 6th or 7th week of embryonic development. The case is reported of a 28-year-old man with bilateral aplasia of the external ear, bilateral aplasia of the ear canal, hypoplasia of the mandibula, severe thoracic scoliosis, and ventricular septal defect with pulmonary hypertension. He was admitted with dyspnea on exertion, syncope, and severe cyanosis. Cardiac catheterization revealed severe pulmonary hypertension with moderate right-to-left and slightly left-to-right shunt (Eisenmenger syndrome). Right and left ventricular function, as evaluated by angiocardiography, was slightly reduced. Because of the severe hemodynamic alterations, symptomatic therapy with digitalis, repeated venesection, and anticoagulation was initiated.
Rodioimmunoassayable somatostatin (SRIF) was found in acid ethanol extracts from various parts of the gastro-entero-pancreatic (GEP) endocrine system in reptiles, amphibians, teleost bony fish, cartilaginous fish, and jawless fish, as well as in a deuterostomian invertebrate, the tunicate, Ciona intestinalis. The cellular sites could, as a rule, be easily visualized light-microscopically by the peroxidase-anti-peroxidase (PAP) immunocytochemical procedure, using guinea-pig and rabbit antisera against synthetic SRIF. The standard Hellerström-Hellman technique, used to detect argyrophi SRIF-storing D cells, failed to visualize the SRIF cells in teh GEP endocrine system of the tumicate and of the jaw-less fish. Moreover, the results comfirmed the previous description that this technique only exceptionally (and sometimes only after further modifications) gave positive results when applied to the GEP endocrine system of bony fish, amphibians, and reptiles. In cartilaginous fish, however, it worked adequately and confirmed the radio-immunological and immunocytochemical observations. In the mucosa of the alimentary tract and in the parenchyma of its associated glands of one echinoderm and two pelecypod molluscs and one crustacean arthropod no sgns of the occurrence of SRIF-storing cells were observed using the three correlated procedures. In several of these tissues, signs of the occurrence of insulin-producing cells had perviously been observed. Thus, SRIF seems to appear at a later evolutionary stage than insulin. The principal islets (Brockmann corpusles) of the marine teleost fish, Cottus scorpius, had the highest concentrations of radioimmunoassayable SRIF of all the GEP organs and tissues investigated, viz. about 200 ng/mg wet weight. Nevertheless, it was only 1/5 of the actual insulin content.