Molecular interactions of guidance receptors acting in early cortical development

The development of a layered cortex requires tightly regulated cell migration events. These are controlled by context-dependent interactions of cell guidance receptors and their ligands, which occur between migrating cells and their environment. In this project, we focus on Unc5 guidance receptors and their FLRT ligands, which together with further binding partners, form combinatorial interactions that instruct the radial migration of neurons in early cortical development.

We will assemble a detailed spatiotemporal map of when/where different protein complexes form during radial migration, determine their atomic structures to obtain mechanistic insight, and design structure-based mutants to specifically target combinatorial ligand binding in vitro and in vivo using mouse models. These results will establish a molecular-level understanding of how radial migration is determined by these guidance receptors.

Research questions:

- Where are different receptor interactions established during cortical migration?

- What are the structural principles that control their interactions?

- How do these interactions direct specific cellular behaviours during radial migration?

The proposal presents an integrated work package using structural biology, protein engineering, proteomics, cell biology, advanced imaging and mouse in vivo technology.

The project creates an outstanding interdisciplinary and international training environment for early career researchers to develop independent academic careers.