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

First Author  Howard L Year  2018
Journal  Development Volume  145
Issue  22 PubMed ID  30337376
Mgi Jnum  J:272611 Mgi Id  MGI:6284197
Doi  10.1242/dev.165936 Citation  Howard L, et al. (2018) TWE-PRIL reverse signalling suppresses sympathetic axon growth and tissue innervation. Development 145(22):dev165936
abstractText  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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