eprintid: 10069932
rev_number: 24
eprint_status: archive
userid: 608
dir: disk0/10/06/99/32
datestamp: 2019-03-12 09:22:33
lastmod: 2021-12-13 01:40:38
status_changed: 2019-03-12 09:22:33
type: article
metadata_visibility: show
creators_name: Dupays, L
creators_name: Towers, N
creators_name: Wood, S
creators_name: David, A
creators_name: Stuckey, DJ
creators_name: Mohun, T
title: Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: FI6
divisions: D11
divisions: G12
note: © 2019 Dupays et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/4.0/
abstract: The homeodomain transcription factor NKX2-5 is known to be essential for both normal heart development and for heart function. But little is yet known about the identities of its downstream effectors or their function during differentiation of cardiac progenitor cells (CPCs). We have used transgenic analysis and CRISPR-mediated ablation to identify a cardiac enhancer of the Furin gene. The Furin gene, encoding a proprotein convertase, is directly repressed by NKX2-5. Deletion of Furin in CPCs is embryonic lethal, with mutant hearts showing a range of abnormalities in the outflow tract. Those defects are associated with a reduction in proliferation and premature differentiation of the CPCs. Deletion of Furin in differentiated cardiomyocytes results in viable adult mutant mice showing an elongation of the PR interval, a phenotype that is consistent with the phenotype of mice and human mutant for Nkx2-5. Our results show that Furin mediate some aspects of Nkx2-5 function in the heart.
date: 2019
date_type: published
official_url: https://doi.org/10.1371/journal.pone.0212992
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1637933
doi: 10.1371/journal.pone.0212992
pii: PONE-D-18-26720
lyricists_name: David, Anna
lyricists_name: Stuckey, Daniel
lyricists_id: ADAVI52
lyricists_id: DSTUC39
actors_name: Joyce, Sophia
actors_id: SJOYC12
actors_role: owner
full_text_status: public
publication: PLoS One
volume: 14
number: 3
article_number: e0212992
event_location: United States
issn: 1932-6203
citation:        Dupays, L;    Towers, N;    Wood, S;    David, A;    Stuckey, DJ;    Mohun, T;      (2019)    Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.                   PLoS One , 14  (3)    , Article e0212992.  10.1371/journal.pone.0212992 <https://doi.org/10.1371/journal.pone.0212992>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10069932/1/Furin%2C%20a%20transcriptional%20target%20of%20NKX2-5%2C%20has%20an%20essential%20role%20in%20heart%20development%20and%20function.pdf