Targeting focal adhesions and the actin cytoskeleton to promote axonal regeneration

• Applicant: Juliane Schiweck
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 516738066

Injuries to the adult central nervous system (CNS) often result in permanent disabilities. Whereas adult peripheral nervous system (PNS) neurons retain some regenerative capacities, CNS neurons lose their ability to regenerate axons.What are the differences between CNS neurons and PNS neurons that affect their regenerative capacities? In 3-dimensional cultures, CNS axon growth is achieved in an amoeboid manner that depends on microtubule protrusion. However, it is not yet clear which mechanisms are employed by PNS neurons to drive axon growth, in particular, on the level of the cytoskeleton. Our preliminary work suggests that PNS neurons depend on actin and focal adhesions for axon growth. We will build on these findings and elucidate the role of three candidate proteins in axon regeneration. All three candidate proteins, namely Drebrin, Kindlin-2 and focal adhesion kinase (FAK), are closely related to focal adhesion formation and dynamics of the actin cytoskeleton. We will then test these three candidate proteins for their potential to drive axon regeneration in the CNS after spinal cord injury. Together, this study will uncover basic mechanisms underlying the growth of PNS axons and elucidate how focal adhesions and the actin cytoskeleton contribute to axonal growth.

• DFG Programme: WBP Position