Eph/ephrin signalling in the developing brain is regulated by tissue stiffness

Sipkova J, Franze K (2025)

Publication Status: Submitted

Publication Type: Unpublished / Preprint

Future Publication Type: Journal article

Publication year: 2025

DOI: 10.1101/2024.02.15.580461

Abstract

Eph receptors and their membrane-bound ligands, ephrins, provide key signals in many biological processes, such as cell proliferation, cell motility and cell sorting at tissue boundaries. However, despite immense progress in our understanding of Eph/ephrin signalling, there are still discrepancies between in vitro and in vivo work, and the regulation of Eph/ephrin signalling remains incompletely understood. Since a major difference between in vivo and most in vitro experiments is the stiffness of the cellular environment, we here investigated the interplay between tissue mechanics and Eph/ephrin signalling using the Xenopus laevis optic pathway as a model system. Xenopus retinal neurons cultured on soft substrates mechanically resembling brain tissue showed the opposite response to ephrinB1 compared to those cultured on glass. In vivo atomic force microscopy (AFM)-based stiffness mapping revealed that the visual area of the Xenopus brain, the optic tectum, becomes mechanically heterogeneous during its innervation by axons of retinal neurons. The resulting stiffness gradient correlated with both a cell density gradient and expression patterns of EphB and ephrinB family members. Exposing ex vivo brains to stiffer matrices or locally stiffening the optic tectum in vivo led to an increase in EphB2 expression in the optic tectum, indicating that tissue mechanics is an important regulator of Eph/ephrin signalling. Similar mechanisms are likely to be involved in the development and diseases of many other organ systems.

Authors with CRIS profile

Kristian Franze Lehrstuhl für Medizinische Physik und Mikrogewebetechnik (IMP)

Additional Organisation(s)

Sonderforschungsbereich 1540: Erforschung der Mechanik des Gehirns (EBM): Verständnis, Engineering und Nutzung mechanischer Eigenschaften und Signale in der Entwicklung, Physiologie und Pathologie des zentralen Nervensystems

Involved external institutions

University of Cambridge GB United Kingdom (GB)

How to cite

APA:

Sipkova, J., & Franze, K. (2025). Eph/ephrin signalling in the developing brain is regulated by tissue stiffness. (Unpublished, Submitted).

MLA:

Sipkova, Jana, and Kristian Franze. Eph/ephrin signalling in the developing brain is regulated by tissue stiffness. Unpublished, Submitted. 2025.

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