The study of the morphological basis of neuronal function remains a subject of tremendous fascination and a key to better understanding of the nervous system. Unraveling the variety of neuronal circuits and their interactions with peripheral sensors and effector organs is as much relevant now as it was over 100 years ago in the time of Golgi and Cajal. Neural tract tracing, cell lineage mapping or the study of morphological plasticity of dendritic spines and axonal arbors all require advanced neuromorphological and imaging techniques.
As Gerald Edelman, the American who received the 1972 Nobel Prize in Physiology or Medicine for work on the immune system, once wrote: "If someone held a gun to my head and threatened oblivion if I did not identify the single word most significant for understanding the brain, I would say 'neuroanatomy'. Indeed, perhaps the most important general observation that can be made about the brain is that its anatomy is the most important thing about it."
However, as Georg F. Striedter in his insightful book 'Principles of Brain Evolution' puts it, "reconstructions ... are interesting and important but, ultimately, they are not enough. Henri Poincaré, the French mathematician and philosopher, clearly expressed this sentiment: 'Science is built with facts, as a house is built with stones; but a collection of facts is no more a science than a pile of stones is a house ... Above all, the scientist must make predictions.'"
Anatomists make predictions about form, since 'form follows function'. This is the credo of the great architect Louis Sullivan (1896): "Whether it be the sweeping eagle in his flight, or the open apple-blossom, the toiling work-horse, the blithe swan, the branching oak, the winding stream at its base, the drifting clouds, over all the coursing sun, form ever follows function, and this is the law. Where function does not change, form does not change."
Our research addresses the morphological consequences of intercellular communication. Growth factors represent a well defined group of signaling molecules that induce changes in form and function of neurons or glial cells. Our goal is to identify targets that may be modulated pharmacologically or genetically to maintain neuronal integrity, stimulate axon regeneration or prevent pathological cellular proliferation in various neurological disorders.
Fibroblast growth factor (FGF) receptor signaling is in the focus of our projects. We have recently analyzed the differential effects of subcellular FGFR1 signaling on neurite outgrowth using optogenetics (Csanaky et al. 2019). Moreover, we have demonstrated that blocking negative feedback inhibitors of FGF signaling such as Sprouty2 promotes axon regeneration and neuronal survival in neurological disease models of the peripheral and central nervous system. Sprouty2 is also important for cell proliferation and tumorigenicity in the brain. Targeting this inhibitor of receptor tyrosine kinase signaling causes excessive ERK activation and sensitizes glioblastoma cells to DNA damage response that eventually leads to decreased proliferation and reduced tumorigenic capacity. For a summary of the function of Sprouty2 in the adult nervous system see our recent review article here.