Division Cell and Developmental Biology
Multipotent stem cells have to 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 differentiation of a stem cell are thought to involve an interplay between extracellular and intracellular cues. How this is achieved is of fundamental importance not only to basic biologists but also with regard to the potential medical use of stem cells for cell replacement therapies and disease modeling.
In our laboratory, we have been studying the development of the neural crest, a transient population of cells in higher vertebrates that emigrates from the developing neural tube to generate most of the peripheral nervous system and a variety of non-neural structures. Among fate-restricted cells, the neural crest harbors many cells termed neural crest stem cells (NCSCs) that display self-renewal capacity and multipotency in clonal cell culture assays. Intriguingly, we have been able to isolate cells very similar to NCSCs from neural crest-derived structures during fetal development and even from adult tissues such as the skin. Thus, neural crest-derived cells with stem cell properties persist throughout development and postnatal stages.
Using functional assays in cell culture in conjunction with genetic approaches in the mouse, such as conditional, tissue-specific gene ablation in vivo, we have been characterizing a plethora of transcription factors and signaling pathways that regulate self-renewal and fate decisions in NCSCs. Moreover, we apply our expertise and tools to the analysis of neural stem cells from the CNS, which enables us to elucidate similarities and differences between distinct types of stem cells with neural potential.
Finally, the basic scientific questions addressed in our studies serve as foundation for more applied stem cell research that we perform together with various collaborators and that include potential therapeutic applications of adult neural crest-derived stem cells and the study of disease mechanisms involving aberrant neural crest stem cell development and tumor formation. Indeed, in human melanoma cells and genetic mouse models of melanoma, we have been able to demonstrate a crucial role of stem cell features for tumor initiation, growth, and metastasis formation. Thus, studying processes of normal stem cell development is a promising path towards the elucidation of mechanisms implicated in tumorigenesis.