Dr. Tien-Chen (Dennis) Lin, Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

Seminar Room MPZPM (0.125), Kussmaulallee 2
Location Details

Abstract
Developing neurons initially extend several equivalent neurites, yet ultimately specify only one as the axon. How this symmetry is broken and how transient cytoskeletal dynamics are converted into stable neuronal polarity remain fundamental questions in neurobiology.
We found that neuronal polarization is preceded by a soma-initiated cytoskeletal oscillator. Periodic ARP2/3-dependent actin remodeling at the soma reorganizes a cell-wide actomyosin network and generates actin waves that coordinate extension and retraction among neurites. When a wave reaches a neurite tip, local ARP2/3 activity counteracts actomyosin contractility, allowing microtubule-dependent protrusion and transient neurite extension. In contrast, global actomyosin activity restrains competing neurites and limits axon number.
Using live imaging, genetic loss of ARP3, optogenetic manipulation, local pharmacological perturbations, and cytoskeletal ultrastructure analysis, we show that ARP2/3 and myosin II form opposing cytoskeletal systems that control whether neurites retract or extend. Loss of ARP2/3 causes actomyosin dominance, microtubule compression and buckling, and failure of axon formation, whereas inhibition of myosin II restores persistent growth even in the absence of ARP2/3. Polarization occurs when one neurite becomes resistant to this global contractile constraint and escapes the oscillatory regime into persistent axonal growth.
I will conclude by discussing the questions that follow from this mechanism: when does a transient growth advantage become a stable axonal identity, what preserves that bias after structural perturbation, and how is the one-axon state maintained once the initial cytoskeletal oscillator has been left behind?