Long-range Ret retrograde signaling drives subtype fate and functional identity in a sensory circuit
Year: 2026
Type: preprint
Abstract: During development, neurons extend axons to appropriate targets and acquire distinct molecular and functional identities. Neurotrophins use retrograde signaling to regulate axon targeting and neuronal survival, yet whether this signaling also instructs functional neuronal subtype maturation remains poorly understood. Using the mechanosensory circuit of the zebrafish posterior lateral line (pLL), we investigate two transient neuronal subtypes, pioneers and followers. Their progenitors initially adopt a follower-like state, with a subset transitioning to pioneers that express high levels of the Gdnf receptor Ret. Pioneers project axons early and preferentially innervate distal targets with distinct postsynaptic physiological properties, whereas low-Ret followers project later to proximal targets. We find that pioneer-derived terminals are significantly less responsive to sensory stimulation than follower-derived terminals, revealing functional specialization between these neuronal subtypes. We show that long-range Ret signaling is required to stabilize pioneer identity and establish subtype-specific physiological properties. Loss of Ret drives transcriptional reversion toward the follower program and convergence of postsynaptic physiology. These findings identify retrograde Ret signaling as a mechanism that couples target-derived cues to neuronal identity and functional circuit diversification.
Source: Research Square
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7203991676