Our motivation
A growing body of evidence suggests that perturbation of interneuron development can result in a variety of complex neuropsychiatric disorders, including autism, bipolar disorder, and schizophrenia. Thus, elucidating how interneurons develop and integrate into canonical brain circuits is crucial for understanding the brain in both health and disease. One promising approach to unravelling the complexity of the differentiated brain is to understand how diverse cell types are created during development. Deciphering the rules that govern how cortical interneuron subtypes acquire their specific intrinsic features and the ability to innervate the appropriate postsynaptic partners and cellular compartments is essential for understanding functional aspects of adult brain organization.
Our Goals
The brain relies on an enormous diversity of local interneurons to form specialized circuits with remarkable processing capacities. Yet how different interneuron types emerge during development and integrate into functional circuits remains unclear. We have started to elucidate the developmental gene expression cascades within mitotic progenitors and postmitotic precursors that result in the generation of differentiated types of cortical interneurons. These results set the stage for a number of fascinating studies examining the respective roles of lineage and environmental factors during cell- fate decisions. The following key questions arise:
- How much of a neuron’s fate is determined by cell-intrinsic genetic programs at the progenitor stage, versus extrinsic factors such as brain activity during and after migration?
- Which genetic mechanisms allow environmental factors to influence cell type diversification, thereby enabling a high degree of flexibility for mammalian organisms to adapt to the external world?
- What are the key transcription factors that regulate cell fate-decisions and how do they relate to psychiatric disorders?
Our approach
Recent experimental advances in high-throughput RNA sequencing (RNA-seq) at the single-cell level have opened up tremendous opportunities to fundamentally advance our understanding of developmental processes. During development, each cell makes independent fate decisions by integrating a wide array of signals from an environment composed of other cells and responds by executing a complex choreography of gene expression cascades. Single-cell RNA-sequencing carried out over developmental time and combined with powerful computational and statistical methods has allowed us to begin to unravel these processes. It is only now that we can design and implement experimental strategies to merge viral genetics with single cell transcriptomics.
In the mayerlab we are using genetic fate mapping strategies combined with statistical and machine learning-based methods, to reconstruct developmental trajectories and we are building an integrated framework to understand how a cell’s spatial localization, epigenomic landscape, parental lineage and neural network activity influence its behavior and fate.
COLLABORATIVE RESEARCH
The MPI-BI is embedded in a research campus that offers interactive collaboration with a large number of institutes and research groups across Munich, including the MPIs of Biochemistry and Psychiatry, the Ludwig-Maximilian University, the Technical University and the Helmholtz Zentrum. We are excited to actively participate in the following research networks:
