POSTPONED Dynamic control of neural proliferation zones in the zebrafish larval thalamus

Status: This talk is in preparation - details may change

This lecture is postponed due to Coronavirus travel restrictions.

Proper growth of the vertebrate brain requires well balanced neural stem cell proliferation, progenitor plasticity, and neurogenesis. Fundamental mechanisms controlling these processes include SoxB1 transcription factors in neural stem cells, and Delta/Notch signaling as well as HES/HER transcription factors in neurogenesis. The larval zebrafish brain is an excellent model to study the regulation of these processes, when neural proliferation zones develop from proliferating neuroepithelium, and later organize into stem cell niche-like structures. We chose the thalamic proliferation zones for their high neurogenic activity and easy optical accessibility in vivo. Using targeted genetic approaches, we elucidate regulatory networks controlling neural stem and progenitor cells. In addition, using CRISPR/Cas9 knock-in fluorescent tagging of endogenous regulators and in vivo light sheet microscopy, we investigate the temporal dynamics of regulation. In contrast to previous studies, which focus on Delta-Notch dependent non cell-autonomous control of progenitor cells, our data reveal a dynamic, cell-autonomous and Notch-independent mechanism that controls neural stem cells. We developed control-of-function tools to manipulate expression in stem cells in the proliferation zone, and reveal surprising robustness of the system against perturbations. We employ a mathematical model to understand dynamic parameters of the neural stem cell regulatory system.