Przemko Tylżanowski's Group

Embryonic development is a fascinating process requiring a very precise spatiotemporal regulation of cellular proliferation and subsequent differentiation. Nonetheless, it is apparent that not a single cascade but rather regulatory networks encompassing very divergent signaling pathways are required for the successful completion of the developmental program. There are a few model systems addressing experimentally these issues and the developing vertebrate limb is one of the more popular ones. It not only permits studying the embryonic events, but also allows investigating pathological and repair processes in postnatal life.
Our research focuses on two aspects of joint and skeletal biology. We investigate the molecular and cellular events governing the formation of the vertebrate limb using developmental models. We also, using stem cell technology, are exploring the possibility of creating cell populations that have the ability to rebuild bone, cartilage and eventually the full joint and growing limb in vitro.

This theme encompasses the investigation of the function of novel genes associated with joint formation and/or disease using zebrafish and chick developmental models. We use several strategies to accomplish that goal. In one of them a large scale collaborative, TREAT-OA (FP7) used Genome Wide Association Studies (GWAS) to identify in patient cohorts several candidate genes associated with osteoarthritis including the COG5 gene cluster consisting of six genes (BCAP29, COG5, DS4L, GR22, HBP1and PRKAR2B). At present there is not sufficient information available permitting to associate any of the genes with known signaling networks. Consequently, we have embarked on the in vivo functional characterization of these genes. For the pathway discovery we use the developing zebrafish model organism.
Another strategy uses human genetics to identify genes and/or mutations resulting in hereditary skeletal malformations (in collaboration with the Center for Human Genetics KU Leuven). Using this approach we have recently identified, using chick model system, the mechanism underlying a synpolydactyly in patients carrying HOXD13 mutations.

To understand the molecular aspects of limb development we also explore the function of Wnt and Bone Morphogenetic Protein regulated events. Specifically, using various mouse genetic models, we investigate the delicate balances between these ligands and their antagonists, FRZB and noggin respectively, and their regulatory function in limb patterning and osteochondrogenic differentiation.