The molecular regulation of the musculoskeletal system development
The establishment of the musculoskeletal system is important from the evolutionary, developmental and biomedical perspective.
The reconfiguration of the musculoskeletal system of the head was tremendously important process during the evolutionary transition from jawless to jawed vertebrates. The arrangement of cartilage, dermal bones, and muscles that organize the musculoskeletal system, takes place during the embryonic development. Stability and functionality of this complex depends on the skeletal joints, ligaments and tendons.
In our project, we are identifying early markers for various musculoskeletal structures by identifying novel regulatory elements of genes expressed in joints, tendons and ligaments, and then testing them in model organisms such as zebrafish. Our goal is to find hitherto unknown regulatory elements that regulate unique expression patterns and follow their role during the development of the musculoskeletal system. Understanding this can give us new insights into processes that explain the morphological changes of vertebrate tissues during evolution and also provide possible strategies for inducing healing and regeneration processes in joints, tendons and ligaments.
3D morphology of the cells and tissues during normal development of the zebrafish skeleton and in the disease models
Using a revolutionary phase-contrast synchrotron X-ray microtomography, we are studying three-dimensional (3D) morphology and histology of cartilage and other skeletal tissues down to individual cells. By using the CRISPR/Ca9 genome editing technology, we generate disease models for rare human skeletal dysplasias in zebrafish and compare the cell organization in 3D between the disease model and the normal development. We apply machine learning to analyze the cells in the generated large image datasets.
Molecules defining the diversity of mineralized tissues in vertebrates
Mineralized tissues like dentine and enamel are crucially important for the proper function of teeth and dermal odontodes in vertebrates. These elements always form at the interface between epithelium and mesenchyme. The mesenchyme normally differentiates into odontoblasts, which deposit dentine matrix, whereas epithelium differentiates into ameloblasts depositing enamel matrix. During the mineralization process the matrix proteins are degraded and exchanged with hydroxyapatite crystals.
The teeth of tetrapods and lobe-finned fishes are covered with dentine and enamel, but these are just two among a much greater variety of mineralized odontode tissues described in vertebrates. For example, ray-finned fishes have scales covered with ganoine and acrodin on the teeth, while cartilaginous fishes have enameloid instead of enamel on teeth, scales and fin spines. We are currently lacking knowledge about the identity of these molecules and how they are deposited during the development of mineralized tissues.
During our project we are comparing the subsets of the genes involved in mineralized tissue development between different vertebrate genomes. We are also identifying the mineralized tissues where these genes are expressed and are looking at the developmental programs behind the deposition of different types of tissue layers. Our study can help to explain the genetic basis underlying the diversity of mineralized tissues in different groups of fishes and provide an understanding of the formation of the various mineralized tissues during the evolution of several groups of basal vertebrates.