In vertebrates, multipotent stem cells generate various differentiated cell types in correct number and sequence and are responsible for tissue formation, homeostasis, and regeneration. The cellular and molecular processes that control stem cells involve an interplay between extracellular and intracellular cues as well as genetic and epigenetic factors. How this is achieved is of fundamental importance not only to basic biologists but also with regard to the potential use of stem cells for regenerative medicine and disease modeling.
Genetic approaches in mouse model systems combined with cell biological assays and comprehensive expression analyses have allowed us to identify mechanisms regulating stem cells in the developing vertebrate embryo. Our favourite research topic is how self-renewal and lineage-specific differentiation are controlled in neural crest stem cells. These cells have a very broad developmental potential and give rise to multiple cell types in our body, including most of the peripheral nervous system, craniofacial bone and cartilage, and melanocytes. Using conditional and inducible gene deletion as well as in vivo lineage tracing methods, we have been able to demonstrate multipotency of neural crest cells in vivo, to determine regulatory factors controlling stem cell maintenance vs. lineage specification, and to establish mouse models of congenital diseases.
In addition, our research led to the identification and characterization of adult neural crest-derived stem cells and their implication in tissue regeneration and tumor formation. In particular, using human cells and genetic mouse models, we showed that melanoma initiation, growth, and disease progression involve many genetic and epigenetic mechanisms also active and required for proper development of normal neural crest stem cells. This line of research provides new insights into melanoma biology and may open new avenues for treatment.