The research group on embryonic neurogenesis (head: Prof. Dr. Alexander Storch) focuses on neuronal plasticity during brain development. The aim of our work is to investigate the influence of oxygen on embryonic neural stem cells and the formation of different brain regions to elucidate the underlying mechanism of oxygen-dependent neurogenesis.

Oxygen is probably the most important gas for our survival and plays a major role in our energy metabolism. However, it also acts as an important signal factor for various cellular processes from the formation of new blood cells to brain development. To regulate these processes, so-called hypoxia inducible factors (HIFs) are produced in our body cells. William G. Kaelin, Peter J. Ratcliffe and Gregg L. Semenza were awarded the Nobel Prize for Medicine in 2019 for the discovery of these HIFs and their underlying mechanism of action. In short, HIF proteins are permanently expressed in our cells, but are immediately degraded under normoxic conditions. A reduced oxygen level, however, slows down the degradation of HIF proteins, so that they in turn can regulate the expression of other nuclear genes.

Since it has long been known that oxygen also influences brain development, it seems likely that the mechanism via HIFs also plays a decisive role in the developing brain. However, how far-reaching this mechanism is and whether it can even be influenced to counteract hypoxic fetal events, for example, is still not well known. Using various in vitro and in vivo methods, we analyze cellular mechanisms in both neuron and stem cell cultures as well as effects on embryonic neuronal plasticity in genetically modified in vivo models in which we can specifically switch off the HIF subunits (HIF1a and HIF2a). In order to simulate different oxygen conditions, we can also perform these experiments in hypoxic or hyperoxic atmosphere.

The current projects are particularly concerned with the perinatal regulation of brain structure after hypoxic and hyperoxic events during brain development.

1. Markert, F., L. Müller, K. Badstübner-Meeske & A. Storch (2020) Early Chronic Intermittent Maternal Hyperoxygenation Impairs Cortical Development by Inhibition of Pax6-Positive Apical Progenitor Cell Proliferation. J Neuropathol Exp Neurol.
2. Fauser, M., G. Weselek, C. Hauptmann, F. Markert, M. Gerlach, A. Hermann & A. Storch (2020) Catecholaminergic Innervation of Periventricular Neurogenic Regions of the Developing Mouse Brain. Front Neuroanat.
3. Wagenfuhr, L., A. K. Meyer, L. Marrone & A. Storch (2016) Oxygen Tension Within the Neurogenic Niche Regulates Dopaminergic Neurogenesis in the Developing Midbrain. Stem Cells Dev, 25, 227-38.
4. Wagenfuhr, L., A. K. Meyer, L. Braunschweig, L. Marrone & A. Storch (2015) Brain oxygen tension controls the expansion of outer subventricular zone-like basal progenitors in the developing mouse brain. Development, 142, 2904-15.
5. Braunschweig, L., A. K. Meyer, L. Wagenfuhr & A. Storch (2015) Oxygen regulates proliferation of neural stem cells through Wnt/beta-catenin signalling. Mol Cell Neurosci, 67, 84-92.