Novel mechanisms of neurogenesis - from centrosome to engineering migration

Title Novel mechanisms of neurogenesis - from centrosome to engineering migration
Acronym NeuroCentro
Start date 2020-10-01
End date 2025-09-30
Sponsor European Research Council - Advanced Grant (ERC-AdG)
Institution Helmholtz Zentrum München

Associated cell lines

Project Description

The centrosome is a crucial cellular organelle involved in many functions especially during development where it acts to regulate key processes, such as cell division, cilia formation and cell migration. While many mutations in centrosome-associated proteins lead to diseases often predominantly affecting the brain, the basis for this specificity is in most cases not known. Likewise, basic aspects of centrosome biology, such as the role of RNAs at the centrosome, are largely unknown. Our recent discovery of novel centrosome-associated proteins in human neural stem cells revealed specific RNA-binding proteins at the sub-distal appendages of centrosomes with significant and selective associations to periventricular heterotopia (PH), a neuronal migration disorder. This provides a unique entry point to explore the fundamental questions associated with the role of RNAs and RNA-binding proteins at the centrosome and their contribution to neurodevelopmental disorders. We will further explore changes in centrosome composition from NSCs to young migratory neurons and identify the role of the centrosome in neuronal subtype-specific migration modes using the novel centrosome protein Akna as entry point. We will utilize our advanced tools for dCas9 multiplexed transcriptional engineering to restore centrosome function of ectopic neurons and revert migration defects causing PH.