Forschung

The central nervous system is arguably our most complex and least understood organ. Billions of neurons and glia are organized into elaborate neural circuits thereby forming the structural basis for learning, memory and complex behavior. Our laboratory uses transgenic mouse models and human pluripotent stem cell-derived models of brain development to unravel the molecular and cell biological mechanisms underlying human brain development and stem cell-dependent plasticity in the adult brain.

Adult neurogenesis

Learning and adjusting behavior to new situations is a crucial ability to master our daily life. Our brain enables us to do so because it is remarkably plastic: Synaptic connections can be adjusted in response to environmental cues throughout life. Even entire neurons can be added to already existing circuits in the adult brain. This extraordinary form of brain plasticity – adult neurogenesis – takes place in specialized niches of the brain, which harbor a unique environment suited to form new neurons from resident stem cells. Adult neurogenesis serves important functions in memory formation, e.g. in spatial orientation, but needs to be tightly controlled. Aging or diseases like epilepsy and Alzheimer’s disease can increase or decrease the rate of adult neurogenesis with consequences on memory formation. Therefore, a main focus of our research is to study molecular mechanisms that control adult neurogenesis. We use transgenic mouse models and primary cell culture systems to investigate how transcription factors, cell metabolism, signaling molecules or environmental stimuli (e.g. exercise or stress) regulate the generation of adult-born neurons from stem cells and their differentiation into mature neurons.

Genetic causes of neurodevelopmental diseases

Brain development is a highly complex process during which more than 16 billion neurons need to be generated at exactly the right time, place and number. During maturation, this vast number of neurons forms more than 10¹⁴ synapses to set up functioning neuronal circuits. It is not surprising that mutations in neurodevelopmental genes can disrupt this complicated process at any time in development. As a consequence, patients carrying such mutations often suffer from intellectual disability or an increased susceptibility to neuropsychiatric diseases. The underlying molecular mechanisms are, however, poorly understood. We use animal and stem cell-based human models to study the effects of mutated, dysfunctional neurodevelopmental genes on the major steps in neurodevelopment – like the generation of neural progenitors from stem cells and their differentiation into mature neurons.