Skip to main content

Chromatin states in neurogenesis – from understanding chromatin loops to eliciting neurogenesis for repair

Objective

The mechanisms regulating neural stem cells and their progression to neurogenesis are important not only to understand brain development and evolution, but also to elicit neurogenesis after brain injury. Our recent findings imply novel chromatin-associated proteins in the regulation of neural stem cell fate and neurogenesis. Therefore this project aims to understand the molecular mechanisms of how these factors regulate neurogenesis in developing and adult mice (Aim1) and implement this knowledge for reprogramming glia into neurons after brain injury (Aim2). This will be pursued in mouse models in vivo (2.1) and with human glial cells derived from patient brain resections in vitro (2.2). It is well known that transcription factors need to alter the chromatin structure to achieve transcriptional regulation, but the factors involved in this regulation in neural stem and progenitor cells are still ill understood. Therefore the molecular function of the novel chromatin interacting protein Trnp1 with essential roles in neural stem cell (NSC) fate and the chromatin conformation mediated at neurogenic target genes by Pax6/Brg1-containing BAF complexes will be addressed in Aim1. Combined with genome-wide approaches to determine changes in chromatin conformation at neurogenic target gene sites this will greatly further our understanding of key roles of chromatin conformation in neural stem cells and neurogenesis. In Aim2 Trnp1 promoting neural stem cells fate and later acting neurogenic transcription factors will be used to improve neuronal reprogramming after stab wound injury in the murine brain in vivo and in patient-derived glial cells in vitro. Together with novel strategies to induce chromatin looping in a sequence-specific manner this project will not only advance our knowledge at the frontier of transcriptional regulation in neurogenesis, but also implement highly innovative approaches to utilize this knowledge for neuronal repair by direct reprogramming.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/molecular biology/molecular genetics
  • /natural sciences/biological sciences/neurobiology

Call for proposal

ERC-2013-ADG
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Germany
Activity type
Research Organisations
EU contribution
€ 2 376 560
Principal investigator
Magdalena Götz (Prof.)
Administrative Contact
Jürgen Ertel (Dr.)

Beneficiaries (1)

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany
EU contribution
€ 2 376 560
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Activity type
Research Organisations
Principal investigator
Magdalena Götz (Prof.)
Administrative Contact
Jürgen Ertel (Dr.)