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BioSoft Colloquium:

The physical regulation of axon development and regeneration

Kristian Franze

Neuronal Mechanics, Max Planck Center for Physics and Medicine, Erlangen

Anfang
29.04.2021 11:00 Uhr
Veranstaltungsort
Remote access

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Abstract:

The microtubule (MT) cytoskeleton in neuronal axons is highly oriented with almost all MTs pointing with their growing end (+end) away from the cell body (+end out). Molecular motor proteins rely on this orientation to efficiently transport cellular cargo to the distal regions of the axon. However, the mechanisms underlying this unique MT configuration remain poorly understood.

We here analyzed MT growth behavior with supervised machine learning in Drosophila melanogaster neurons, complemented by an analytical model of MT growth and shrinkage. +end out MTs grew for longer times than –end out MTs, leading to dramatic differences in average MT lengths with –end out MTs being short and unstable. We suggest a simple mechanism that organizes axonal MTs. First, +end out MTs grow longer because of a decrease in crowding in the periphery. Subsequently, the short –end out MTs are transported out of the axon, depolymerize, or reorient, leaving mostly +end out MTs in the axon.

Once MT polarity is established, axons keep growing to their target tissue. In order to move, neurons have to exert forces on and thus mechanically interact with their environment. In the second part, I show that mechanical interactions of neurons with their environment are dynamic and change during development and regeneration.

Using time-lapse in vivo atomic force microscopy-based stiffness mapping, we identified stiffness gradients in the developing Xenopus brain which contribute to regulating axon growth and pathfinding. Interfering with brain stiffness and mechanosensitive ion channels in vivo both led to similar aberrant neuronal growth patterns with reduced fasciculation and pathfinding errors. Importantly, CNS tissue significantly softened after traumatic injuries.

Ultimately, mechanical signals not only directly impacted neuronal growth but also indirectly by regulating neuronal responses to and the availability of chemical guidance cues, strongly suggesting that chemical and mechanical signaling pathways are intimately linked, and that their interaction is crucial for neuronal development.


Kontakt

Dr. Dmitry Fedosov
Telefon: +49 2461 61-2972
Fax: +49 2461 61-3180
E-Mail: d.fedosov@fz-juelich.de