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Morphological and molecular characterization of developing vertebral fusions using a teleost model.

ABSTRACT: BACKGROUND: Spinal disorders are a major cause of disability for humans and an important health problem for intensively farmed animals. Experiments have shown that vertebral deformities present a complex but comparable etiology across species. However, the underlying molecular mechanisms involved in bone deformities are still far from understood. To further explicate the mechanisms involved, we have examined the fundamental aspects of bone metabolism and pathogenesis of vertebral fusions in Atlantic salmon (Salmo salar). RESULTS: Experimentally, juvenile salmon were subjected to hyperthermic conditions where more than 28% developed fused vertebral bodies. To characterize the fusion process we analyzed an intermediate and a terminal stage of the pathology by using x-ray, histology, immunohistochemistry, real-time quantitative PCR and in situ hybridization. At early stage in the fusion process, disorganized and proliferating osteoblasts were prominent at the growth zones of the vertebral body endplates. PCNA positive cells further extended along the rims of fusing vertebral bodies. During the developing pathology, the marked border between the osteoblast growth zones and the chondrocytic areas connected to the arches became less distinct, as proliferating cells and chondrocytes blended through an intermediate zone. This cell proliferation appeared to be closely linked to fusion of opposing arch centra. During the fusion process a metaplastic shift appeared in the arch centra where cells in the intermediate zone between osteoblasts and chondrocytes co-expressed mixed signals of chondrogenic and osteogenic markers. A similar shift also occurred in the notochord where proliferating chordoblasts changed transcription profile from chondrogenic to also include osteogenic marker genes. In progressed fusions, arch centra and intervertebral space mineralized. CONCLUSION: Loss of cell integrity through cell proliferation and metaplastic shifts seem to be key events in the fusion process. The fusion process involves molecular regulation and cellular changes similar to those found in mammalian deformities, indicating that salmon is suitable for studying general bone development and to be a comparative model for spinal deformities.

SUBMITTER: Ytteborg E

PROVIDER: S-EPMC2909226 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Morphological and molecular characterization of developing vertebral fusions using a teleost model.

Ytteborg Elisabeth E Torgersen Jacob J Baeverfjord Grete G Takle Harald H

BMC physiology 20100706

<h4>Background</h4>Spinal disorders are a major cause of disability for humans and an important health problem for intensively farmed animals. Experiments have shown that vertebral deformities present a complex but comparable etiology across species. However, the underlying molecular mechanisms involved in bone deformities are still far from understood. To further explicate the mechanisms involved, we have examined the fundamental aspects of bone metabolism and pathogenesis of vertebral fusions ...[more]

PMID: 20604916

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Project description:BackgroundMorphological integration refers to the tendency of anatomical structures to show correlated variations because they develop in response to shared developmental processes or function in concert with other structures. The objective of this study was to determine the relationships between the dimensions of different cranial-cervical-facial structures in patients with Down syndrome (DS).MethodologyThe study group consisted of 41 individuals with DS who had undergone cone-beam computed tomography (CBCT) at the Dental Radiology Unit of the University of Santiago de Compostela (Spain). In the historical archive of this same unit, 41 CBCTs belonging to individuals with no known systemic disorders or severe malformations of the maxillofacial region were selected, forming an age and sex-matched control group. Twenty-nine measurements were performed on each participant's CBCT images, which were grouped into three blocks: atlantoaxial dimensions, craniovertebral dimensions and cephalometric dimensions. To determine whether there were significant differences between the dimensions obtained in the DS and control groups, we applied multiple analysis of variance and linear discriminant analysis tests. The analysis of the association between blocks (in pairs) was performed with the canonical correlation analysis test.ResultsThe dimensions evaluated in the three blocks of variables of individuals with DS differ significantly from those of nonsyndromic controls (p < 0.001). The highest discriminative capacity to identify controls and patients with DS was obtained with the cephalometric dimensions (87.5%). With regard to the association between blocks (two-by-two measurements), we found no significant relationship in the DS group. However, we confirmed a statistically significant correlation between all pairs of blocks of variables in the controls, especially between the atlantoaxial and cephalometric dimensions (p < 0.001) and between the craniovertebral and cephalometric dimensions (p < 0.001).ConclusionsOur results confirm a very poor morphological integration of the cranial-cervical-maxillary complex in individuals with DS. This finding reinforces the proposal that gene overload enhances the channeling process.

Project description:Efficient seed dispersal in flowering plants is enabled by the development of fruits, which can be either dehiscent or indehiscent. Dehiscent fruits open at maturity to shatter the seeds, while indehiscent fruits do not open and the seeds are dispersed in various ways. The diversity in fruit morphology and seed shattering mechanisms is enormous within the flowering plants. How these different fruit types develop and which molecular networks are driving fruit diversification is still largely unknown, despite progress in eudicot model species. The orchid family, known for its astonishing floral diversity, displays a huge variation in fruit dehiscence types, which have been poorly investigated. We undertook a combined approach to understand fruit morphology and dehiscence in different orchid species to get more insight into the molecular network that underlies orchid fruit development. We describe fruit development in detail for the epiphytic orchid species Erycina pusilla and compare it to two terrestrial orchid species: Cynorkis fastigiata and Epipactis helleborine. Our anatomical analysis provides further evidence for the split carpel model, which explains the presence of three fertile and three sterile valves in most orchid species. Interesting differences were observed in the lignification patterns of the dehiscence zones. While C. fastigiata and E. helleborine develop a lignified layer at the valve boundaries, E. pusilla fruits did not lignify at these boundaries, but formed a cuticle-like layer instead. We characterized orthologs of fruit-associated MADS-domain transcription factors and of the Arabidopsis dehiscence-related genes INDEHISCENT (IND)/HECATE 3 (HEC3), REPLUMLESS (RPL) and SPATULA (SPT)/ALCATRAZ (ALC) in E. pusilla, and found that the key players of the eudicot fruit regulatory network appear well-conserved in monocots. Protein-protein interaction studies revealed that MADS-domain complexes comprised of FRUITFULL (FUL), SEPALLATA (SEP) and AGAMOUS (AG) /SHATTERPROOF (SHP) orthologs can also be formed in E. pusilla, and that the expression of HEC3, RPL, and SPT can be associated with dehiscence zone development similar to Arabidopsis. Our expression analysis also indicates differences, however, which may underlie fruit divergence.

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Morphological and molecular characterization of developing vertebral fusions using a teleost model.

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Morphological and molecular characterization of developing vertebral fusions using a teleost model.

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