Ongoing research

Conserved cis-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.

The evolution of the lymphatic vasculature in vertebrates (VR Postdoc Virginia Panara)

The lymphatic vasculature is composed of a series of blind ended vessels and has an important function in controlling body fluid homeostasis by absorption from the interstitial tissues. It is also involved in immune cell trafficking and dietary lipid absorption. In humans, defects in lymphatic vasculature, either congenital or caused by trauma, result in a condition known as lymphedema, for which there is currently no cure.

The mammalian lymphatic vasculature has been extensively described, and much is known about its anatomy, physiology and development. However, we have limited knowledge about the evolutionary history of these vessels, and it was only in 2006 that a lymphatic vasculature homologous to the mammalian one was described in Actinopterygii. As of today, it is unclear when the lymphatic vasculature emerged in vertebrates, and what are its evolutionary origins.

In this project, we use a combination of molecular markers, functionality assays and developmental approaches to identify the evolutionary homologs of lymphatic vessels in chondrichthyans and cyclostomes and define their characteristics, in order to shed light on the evolutionary history of this vasculature.

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.