HAND transcription factors are required for neonatal sympathetic neuron survival.

EMBO Reports
Epaminondas DoxakisAlun M Davies

Abstract

Expression of the basic helix-loop-helix transcription factor HAND2 begins early in sympathetic neuron development and is essential for the differentiation of noradrenergic neurons. Here, we show that the expression of HAND2 and related HAND1 are maintained in sympathetic neurons throughout fetal and postnatal development when these neurons depend on target-derived nerve growth factor (NGF) for survival. Short interfering RNA knockdown of endogenous HAND2 and, to a lesser extent, HAND1 in neonatal sympathetic neurons cultured with NGF, reduced the expression of the NGF receptor tyrosine kinase TrkA (tropomyosin-related kinase A), as well as neuronal survival. Chromatin immunoprecipitation analysis showed that NGF promotes HAND2 binding to the TrkA minimal enhancer and that transfection of sympathetic neurons with a TrkA expression plasmid rescued the neurons from HAND knockdown. These findings show that HAND transcription factors have a crucial function in sustaining the survival of neonatal sympathetic neurons with NGF by a feed-forward loop that maintains the expression of TrkA.

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Citations

Mar 8, 2012·Pediatric Cardiology·Joshua W VincentzAnthony B Firulli
Feb 11, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joshua W VincentzAnthony B Firulli
Jun 23, 2011·Annual Review of Neuroscience·Nuria Flames, Oliver Hobert
Jan 19, 2011·Molecular and Cellular Neurosciences·Michael J PellegrinoBeth A Habecker
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Jun 12, 2013·Developmental Biology·Markus TögelAchim Paululat
Nov 20, 2016·Science·I Espinosa-MedinaJ-F Brunet
Sep 16, 2020·Cell and Tissue Research·Uwe ErnsbergerHermann Rohrer
Feb 22, 2021·Ageing Research Reviews·Osvaldo DelbonoMaria Laura Messi

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