Ongoing research

The establishment of the musculoskeletal system is important from the evolutionary, developmental and biomedical perspective. Understanding the musculoskeletal tissue arrangement and important regulatory factors lying behind it can provide new insights into recovery and regeneration of muscles, skeletal elements and connective tissue in age - and sports - related injuries. We are investigating the molecular mechanisms of tendon and ligament development in the head structures of jawed vertebrates. By characterizing the specific markers for connective tissues using zebrafish, we want to establish a novel model for biomedical research of tendons and ligaments.

Another research interest is to compare the mineralization processes in dental tissues. We want to identify the molecular components specifying the morphological and histological biodiversity of mineralized tissues covering teeth and dermal odontodes of jawed vertebrates. Here we start from comparative genomic analysis of mineralization genes in jawed vertebrates and later characterize the role of different extracellular matrix molecules during the establishment of mineralized tissues. This project involves collaboration with the palaeontologists and developmental biologists in order to resolve the evolutionary scenarios of hard tissue development in both extant and fossil vertebrates.

Sophie Sanchez, Uppsala University
Prof. Per E. Ahlberg, Uppsala University
Johan Ledin, Uppsala University
Prof. Masataka Okabe, Jikei University School of Medicine
Mélanie Debiais-Thibaud, Université Montpellier
Jan Štundl, Charles University in Prague

Development of cranial tendons and ligaments in the musculoskeletal system of vertebrates

The establishment of the musculoskeletal system of the head was tremendously important for 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 connective tissue, ligaments and tendons. Studies of the cranial musculoskeletal system paid the least attention to the tendons, since there is no model that allows studying all components simultaneously. In our project we are identifying and characterizing the early markers of these musculoskeletal structures. We want to establish transgenic models that will allow us to position and visualize muscle attachments and ligaments in live zebrafish embryos. These model organisms will be used to study the migration of connective tissue cell lineages during development. The generated model will be a great tool for functional studies of the genes involved in tendon and ligament development and regeneration. We are also studying the regulatory mechanisms in the connective tissue by measuring gene transcript levels and by identifying activated cis regulatory elements during the development of the head. Understanding the connective tissue arrangement and important regulatory factors lying behind it, can provide new insights into tendon and ligament recovery and regeneration.

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.