Axotomy-induced HIF-serotonin signalling axis promotes axon regeneration in C. elegans

Nature Communications
Tanimul AlamKunihiro Matsumoto

Abstract

The molecular mechanisms underlying the ability of axons to regenerate after injury remain poorly understood. Here we show that in Caenorhabditis elegans, axotomy induces ectopic expression of serotonin (5-HT) in axotomized non-serotonergic neurons via HIF-1, a hypoxia-inducible transcription factor, and that 5-HT subsequently promotes axon regeneration by autocrine signalling through the SER-7 5-HT receptor. Furthermore, we identify the rhgf-1 and rga-5 genes, encoding homologues of RhoGEF and RhoGAP, respectively, as regulators of axon regeneration. We demonstrate that one pathway initiated by SER-7 acts upstream of the C. elegans RhoA homolog RHO-1 in neuron regeneration, which functions via G12α and RHGF-1. In this pathway, RHO-1 inhibits diacylglycerol kinase, resulting in an increase in diacylglycerol. SER-7 also promotes axon regeneration by activating the cyclic AMP (cAMP) signalling pathway. Thus, HIF-1-mediated activation of 5-HT signalling promotes axon regeneration by activating both the RhoA and cAMP pathways.

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Citations

Feb 19, 2017·Current Opinion in Genetics & Development·Naoki Hisamoto, Kunihiro Matsumoto
Jul 26, 2018·Journal of Tissue Engineering and Regenerative Medicine·Mireille M J P E SthijnsVanessa L S LaPointe
Nov 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Atrayee BasuAnindya Ghosh-Roy
Nov 8, 2017·Proceedings of the National Academy of Sciences of the United States of America·Zehra C AbayBrent Neumann
Feb 25, 2020·Journal of Biochemistry·Tatsuhiro Shimizu, Naoki Hisamoto
Jan 24, 2017·Genetics·Andrew D ChisholmWilliam G Wadsworth
Mar 21, 2018·Neural Regeneration Research·Daniel Sobrido-CameánAntón Barreiro-Iglesias
Sep 9, 2018·Scientific Reports·Camille A JuźwikAlyson E Fournier
Nov 2, 2019·Cells·David Romeo-GuitartCaty Casas
Feb 3, 2019·Disease Models & Mechanisms·Daniel Sobrido-CameánAntón Barreiro-Iglesias
Dec 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zohar AbergelEinav Gross

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Methods Mentioned

BETA
nucleotide exchange
two-hybrid
GTPases
PCR
transgenic

Software Mentioned

ImageJ
Keyence BZ - X700

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