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Neuroscience› Cellular and Molecular Neuroscience› Axon Guidance and Neuronal Signaling

Axon guidance signalling — EphrinA5 binding to RET receptor tyrosine kinase

Submitted 2026-10-23

Field: Neuroscience › Cellular and Molecular NeuroscienceType: No effect foundArea: axon guidance signallingTarget: EphrinA5 binding to RET receptor tyrosine kinaseStage: preclinical

Hypothesis

EphrinA5 would bind the RET receptor directly, as earlier cell-based assays suggested, which would explain reverse signalling that guides motor axons.

What failed

Zebrafish ephrinA5b bound mouse EphA4 with high affinity, but in vitro it showed no interaction with zebrafish RET.

Broken assumption

EphrinA5 and RET bind each other directly.

Why

The authors suggest that other molecules may be needed for ephrinA5 to signal through RET, which cell-based assays would contain and a purified system would not.

From the published paper: Liu et al. PLoS ONE, 2018. ↗CC BY

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Related failures

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Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.