Resorption and remodelling of skeletal tissues is required for development and growth, mechanical adaptation, repair, and mineral homeostasis of the vertebrate skeleton. Here we review for the first time the current knowledge about resorption and remodelling of the skeleton in teleost fish, the largest and most diverse group of extant vertebrates. Teleost species are increasingly used in aquaculture and as models in biomedical skeletal research. Thus, detailed knowledge is required to establish the differences and similarities between mammalian and teleost skeletal remodelling, and between distantly related species such as zebrafish (Danio rerio) and medaka (Oryzias latipes). The cellular mechanisms of differentiation and activation of osteoclasts and the functions of teleost skeletal remodelling are described. Several characteristics, related to skeletal remodelling, distinguish teleosts from mammals. These characteristics include (a) the absence of osteocytes in most species; (b) the absence of haematopoietic bone marrow tissue; (c) the abundance of small mononucleated osteoclasts performing non-lacunar (smooth) bone resorption, in addition to or instead of multinucleated osteoclasts; and (d) a phosphorus- rather than calcium-driven mineral homeostasis (mainly affecting the postcranial dermal skeleton). Furthermore, (e) skeletal resorption is often absent from particular sites, due to sparse or lacking endochondral ossification. Based on the mode of skeletal remodelling in early ontogeny of all teleosts and in later stages of development of teleosts with acellular bone we suggest a link between acellular bone and the predominance of mononucleated osteoclasts, on the one hand, and cellular bone and multinucleated osteoclasts on the other. The evolutionary origin of skeletal remodelling is discussed and whether mononucleated osteoclasts represent an ancestral type of resorbing cells. Revealing the differentiation and activation of teleost skeletal resorbing cells, in the absence of several factors that trigger mammalian osteoclast differentiation, is a current challenge. Understanding which characters of teleost bone remodelling are derived and which characters are conserved should enhance our understanding of the process in fish and may provide insights into alternative pathways of bone remodelling in mammals.
Dental agenesis is the most common developmental anomaly in humans and is frequently associated with several other oral abnormalities. Whereas the incidence of missing teeth may vary considerably depending on dentition, gender, and demographic or geographic profiles, distinct patterns of agenesis have been detected in the permanent dentition. These frequently involve the last teeth of a class to develop (I2, P2, M3) suggesting a possible link with evolutionary trends. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) involving one (80% of cases), a few (less than 10%) or many teeth (less than 1%), or can be associated with a systemic condition or syndrome (syndromic hypodontia), essentially reflecting the genetically and phenotypically heterogeneity of the condition. Based on our present knowledge of genes and transcription factors that are involved in tooth development, it is assumed that different phenotypic forms are caused by different genes involving different interacting molecular pathways, providing an explanation not only for the wide variety in agenesis patterns but also for associations of dental agenesis with other oral anomalies. At present, the list of genes involved in human non-syndromic hypodontia includes not only those encoding a signaling molecule (TGFA) and transcription factors (MSX1 and PAX9) that play critical roles during early craniofacial development, but also genes coding for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). Our objective was to review the current literature on the molecular mechanisms that are responsible for selective dental agenesis in humans and to present a detailed overview of syndromes with hypodontia and their causative genes. These new perspectives and future challenges in the field of identification of possible candidate genes involved in dental agenesis are discussed.
Osteichthyan and chondrichthyan fish present an astonishing diversity of skeletal and dental tissues that are often difficult to classify into the standard textbook categories of bone, cartilage, dentine and enamel. To address the question of how the tissues of the dermal skeleton evolved from the ancestral situation and gave rise to the diversity actually encountered, we review previous data on the development of a number of dermal skeletal elements (odontodes, teeth and dermal denticles, cranial dermal bones, postcranial dermal plates and scutes, elasmoid and ganoid scales, and fin rays). A comparison of developmental stages at the tissue level usually allows us to identify skeletogenic cell populations as either odontogenic or osteogenic on the basis of the place of formation of their dermal papillae and of the way of deposition of their tissues. Our studies support the evolutionary affinities (1) between odontodes, teeth and denticles, (2) between the ganoid scales of polypterids and the elasmoid scales of teleosts, and (3) to a lesser degree between the different bony elements. There is now ample evidence to ascertain that the tissues of the elasmoid scale are derived from dental and not from bony tissues. This review demonstrates the advantage that can be taken from developmental studies, at the tissue level, to infer evolutionary relationships within the dermal skeleton in chondrichthyans and osteichthyans.
Anterior/posterior (a/p) compression of the vertebral column, referred to as 'short tails', is a recurring event in farmed Atlantic salmon. Like other skeletal deformities, the problem usually becomes evident in a late life phase, too late for preventive measures, making it difficult to understand the aetiology of the disease. We use structural, radiological, histological, and mineral analyses to study 'short tail' adult salmon and to demonstrate that the study of adult fish can provide important insights into earlier developmental processes. 'Short tails' display a/p compressed vertebrae throughout the spine, except for the first post-cranial vertebrae. The vertebral number is unaltered, but the intervertebral space is reduced and the vertebrae are shorter. Compressed vertebrae are characterized by an unchanged central part, altered vertebral end plates (straight instead of funnel-shaped), an atypical inward bending of the vertebral edges, and structural alterations in the intervertebral tissue. The spongiosa is unaffected. The growth zones of adjacent vertebrae fuse and blend towards the intervertebral space into chondrogenic tissue. This tissue produces different types of cartilage, replacing the notochord. The correspondence in location of intervertebral cartilage and deformed vertebral end plates, and the clearly delimited, unaltered, central vertebral parts suggest that the a/p compression of vertebral bodies is a late developmental disorder that may be related to a metaplastic shift of osteogenic tissue into chondrogenic tissue in the vertebral growth zone. Given the lack of evidence for infections, metabolic disorders and/or genetic disorders, we propose that an altered mechanical load could have caused the transformation of the bone growth zones and the concomitant replacement of the intervertebral (notochord) tissue by cartilaginous tissues in the 'short tails' studied here. This hypothesis is supported by the role that notochord cells are known to play in spine development and in maintaining the structure of the intervertebral disk.KEY WORDS: Notochord · Skeletal deformities · Vertebral malformations · Metaplasia · Bone · Salmon · Chondrogenesis Resale or republication not permitted without written consent of the publisherDis Aquat Org 64: [237][238][239][240][241][242][243][244][245][246] 2005 be regarded as undeformed (McKay & Gjerde 1986, Madsen et al. 2000. In Atlantic salmon Salmo salar the pronounced a/p compression of the vertebral column results in a phenotype that is characterized by a reduced fork length (FL) and increased body height, traits that result in a deformity-related high condition factor (CF). These individuals are referred to as 'short tails' (Vågsholm & Djupvik 1998).The appearance of 'short tails' is a recurrent problem in salmon farming. The prevalence can vary from year to year, from region to region, and from cage to cage. Some observations suggest that the prevalence of 'short tails' follows a smolt group, with higher frequencies in groups of fast growth smolts...
The evolutionary links that exist between odontodes and organs that are phylogenetically related to them (teeth and scales) suggest the use of comparative approaches to study these structures. Part one of this review briefly introduces current ideas on how the pattern of odontodes and odontode‐derived tissues has been established during evolution to yield the diversity of odontode‐related organs currently observed in nature in the cranial and postcranial skeleton. This introductory survey is used to highlight aspects of the developmental processes underlying the formation of some of these organs and the resemblance their development bears to odontogenesis. Part two provides a concise survey of the diversity of tooth structure in the different classes of extant vertebrates, in particular with reference to enamel/enameloid and dentine structure, and tooth attachment. Against this background, the current state of knowledge is reviewed with regard to developmental mechanisms involved in non‐mammalian odontogenesis. Common structure and similarities in development demonstrate that teeth and odontode derivatives should not be considered subjects of separate lines of research. On the contrary, results acquired in one of these fields are relevant to the other and may disclose model species that are relevant to studies on mammalian odontogenesis.
Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (β3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs(∗)163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals' fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming β3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that β3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for β3GalT6 in multiple major developmental and pathophysiological processes.
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