Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism.

Animals Cell Proliferation Heart / physiopathology Mice Myocytes, Cardiac / metabolism Receptors, Notch / metabolism Wnt Signaling Pathway / genetics Zebrafish
Notch Wnt cardiac repair cardiomyocyte proliferation heart regeneration notum wif zebrafish

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
15 01 2019
Historique:
received: 06 04 2018
revised: 07 11 2018
accepted: 11 12 2018
entrez: 17 1 2019
pubmed: 17 1 2019
medline: 10 4 2020
Statut: ppublish

Résumé

Previous studies demonstrate that the regenerative zebrafish heart responds to injury by upregulating Notch receptors in the endocardium and epicardium. Moreover, global suppression of Notch activity following injury impairs cardiomyocyte proliferation and induces scarring. However, the lineage-specific requirements for Notch signaling and full array of downstream targets remain unidentified. Here, we demonstrate that inhibition of endocardial Notch signaling following ventricular amputation compromises cardiomyocyte proliferation and stimulates fibrosis. RNA sequencing uncovered reduced levels of two transcripts encoding secreted Wnt antagonists, Wif1 and Notum1b, in Notch-suppressed hearts. Like Notch receptors, wif1 and notum1b are induced following injury in the endocardium and epicardium. Small-molecule-mediated activation of Wnt signaling is sufficient to impair cardiomyocyte proliferation and induce scarring. Last, Wnt pathway suppression partially restored cardiomyocyte proliferation in hearts experiencing endocardial Notch inhibition. Taken together, our data demonstrate that Notch signaling supports cardiomyocyte proliferation by dampening myocardial Wnt activity during zebrafish heart regeneration.

Identifiants

DOI: 10.1016/j.celrep.2018.12.048 PMID: 30650349 PMC: PMC6366857
pubmed: 30650349
pii: S2211-1247(18)31978-8
doi: 10.1016/j.celrep.2018.12.048
pmc: PMC6366857
mid: NIHMS1518820
pii:
doi:

Substances chimiques

Receptors, Notch 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

546-554.e5

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL127067
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139806
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135831
Pays : United States

Informations de copyright

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Long Zhao (L)

Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA.

Raz Ben-Yair (R)

Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA.

Caroline E Burns (CE)

Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: cburns6@mgh.harvard.edu.

C Geoffrey Burns (CG)

Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: gburns@cvrc.mgh.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Endocardial Notch Signaling Promotes...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Endocardial Notch Signaling Promotes...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Endocardial Notch Signaling Promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Endocardial Notch Signaling Promotes...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › Endocardial Notch Signaling Promotes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs Notch › Endocardial Notch Signaling Promotes...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › Endocardial Notch Signaling Promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Cypriniformes › Cyprinidae › Danio zébré › Endocardial Notch Signaling Promotes...