Research Themes

What limits cellular brain plasticity?

Non-mammalian vertebrates regenerate CNS injuries much better than mammals. Yet, the mechanisms that allow or limit CNS regeneration in vertebrates are largely unknown. The regeneration of fish retina, which can regenerate very severe injury, is dependent on the de-differentiation. In contrast, we have found that the brain regeneration potential in zebrafish appears to be limited and directly dependent on the availability of specific neuronal progenitors. Whether the limited progenitor potential is caused by autonomous intrinsic properties or by non-permissive environmental cues remains a mystery.

To answer fundamental questions about the intrinsic properties of neural progenitors and the tissue environment in zebrafish, we use classical developmental biology approaches, such as heterotopic and heterochronic transplantations together with state of art genetic tools, such as lineage tracing, cell specific ablations and cellular reprogramming. Additionally, microarrays and deep sequencing approaches are used to reveal the gene networks that govern brain plasticity.

How neural stem cell niches are established and maintained into adulthood

Most neurons in the vertebrate CNS are generated during embryonic development. However, limited neurogenesis takes place in special microenvironments, stem cell niches, also in the adult brain. How neural stem cell niches are formed and specified during development and how they are maintained post-embryonically is not well-understood. To study common cellular and molecular characteristics of neural stem niches in vertebrates, a comparative approach is used that capitalizes on the abundance of neural stem cells in different brain regions in zebrafish. Novel genetic tools and in vivo imaging are used to trace the developmental origin of the neural stem cell niches from the early germinal zones. The developmental origin and timing of neural stem niche formation can be then linked to known patterning mechanisms and active signaling pathways. Furthermore, microarrays and deep sequencing are used to identify the gene networks involved in stem cell niche development and homeostasis. These networks can then be further functionally tested in vivo.