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TWE-PRIL reverse signalling suppresses sympathetic axon growth and tissue innervation

Research output: Contribution to journalArticle

Laura Howard, Erin Wosnitzka, Darian Okakpu, Matthew A White, Sean Wyatt, Alun M Davies

Original languageEnglish
JournalDevelopment
Volume145
Issue number22
DOIs
Published19 Nov 2018

Bibliographical note

© 2018. Published by The Company of Biologists Ltd.

King's Authors

Abstract

TWE-PRIL is a naturally occurring fusion protein of components of two TNF superfamily members: the extracellular domain of APRIL; and the intracellular and transmembrane domains of TWEAK with no known function. Here, we show that April-/- mice (which lack APRIL and TWE-PRIL) exhibited overgrowth of sympathetic fibres in vivo, and sympathetic neurons cultured from these mice had significantly longer axons than neurons cultured from wild-type littermates. Enhanced axon growth from sympathetic neurons cultured from April-/- mice was prevented by expressing full-length TWE-PRIL in these neurons but not by treating them with soluble APRIL. Soluble APRIL, however, enhanced axon growth from the sympathetic neurons of wild-type mice. siRNA knockdown of TWE-PRIL but not siRNA knockdown of APRIL alone also enhanced axon growth from wild-type sympathetic neurons. Our work reveals the first and physiologically relevant role for TWE-PRIL and suggests that it mediates reverse signalling.

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