Our major interests are concentrated around the idea that peripheral nerves are essential for development of organs since they contribute multipotent cells to the local tissues and serve as delivery routes for progenitors giving rise, for example, to melanocytes, parasympathetic neurons, residential mesenchymal cells in the bone marrow and to dental mesenchymal stem cells. This very fresh field of nerve-associated multipotent cells has been initiated and largely advanced by our lab members. At the moment, there are more than 10 publications from other independent research groups proving and expanding this very new concept. Within very few recent years it became evident that the nerves serve as migratory routes and a niche for the neural crest-like multipotent cells that are recruited, locally expanded and differentiated in a targeted way during specific phases of development and, potentially, in regeneration. This strategy leads to the complexity reduction in pathfinding programs involved in otherwise necessary migratory behavior of neural crest-like precursors. At this particular moment we are intensely investigating the molecular mechanisms explaining how nerve-associated glial cells are recruited in from the nerve surface and produce other cell types also during healing and regeneration. We apply single cell transcriptomics, color multiplexing in genetic tracing as well as functional studies in mouse, chick and zebrafish to address the relationships and molecular similarities between these peripheral glial cells and migratory neural crest populations. Our single cell approach coupled to powerful validation system allows to investigate gene regulatory networks operating during differentiation of crest and glia.
With this state-of-the-art approach we attempt to answer rather fundamental questions about how an individual cell processes information during multiple fate choice. We are addressing and simulating in silico how gene regulatory networks compete, assemble and dissipate within individual cells of the neural crest and glial lineages.
In parallel with this, peripheral nerves are essential for regeneration of the peripheral tissues in all studied vertebrate model systems, especially during appendage regeneration, since Schwann cells detect the damage and secrete the key signals responsible for regenerative blastema formation. The degree of nervous system control over other tissues is incredible, and, as our recent preliminary data show, such control can be responsible for certain craniofacial defects. We also envision that neurons possess the necessary molecular tools to communicate morphogenetic information with associated glial cells to transmit novel types of signals further into peripheral tissues. Knowledge of such signals (spanning the triad neuron-glia-innervated cell) can enormously assist understanding of vitiligo development, some craniofacial abnormalities as well as multiple forms of cancer. We aim to study such molecular systems and heterogeneity of glial cells at single cell level to better explain the connection between nervous system and developing/regenerating organs.
Another interesting question that we are addressing is how the geometry of organs and bodyparts is encoded in genes. What is the role of innervation in particular geometry development? For example, denervated mouse fingers cannot reproduce the original functional shape during regeneration. Therefore, we look into basic principles of morphogenesis and connect them to neurobiology. The best model system in this case is facial development since a large part of the face develops from the neural crest cell. Also, embryonic denervations, nerve-damaging trauma or congenital abnormalities of brain development often strongly affect the facial appearence. We are using transgenic animals, genetic tracing and live imaging to explain how the signals from nervous sustem affect clonal cell behaviour during craniofacial development. However, the role of individual cranial nerves in this process is still enigmatic.