Cited by 139Congenital heart defects researchWnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene Regulation

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Wnt signaling in heart valve development and osteogenic gene induction

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Alfieri, Christina M., Cheek, Jonathan, Chakraborty, Santanu, Yutzey, Katherine E.·2010·Developmental Biology

DOI 10.1016/j.ydbio.2009.11.030PMC PMC2814915

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Abstract

Wnt signaling mediated by beta-catenin has been implicated in early endocardial cushion development, but its roles in later stages of heart valve maturation and homeostasis have not been identified. Multiple Wnt ligands and pathway genes are differentially expressed during heart valve development. At E12.5, Wnt2 is expressed in cushion mesenchyme, whereas Wnt4 and Wnt9b are predominant in overlying endothelial cells. At E17.5, both Wnt3a and Wnt7b are expressed in the remodeling atrioventricular (AV) and semilunar valves. In addition, the TOPGAL Wnt reporter transgene is active throughout the developing AV and semilunar valves at E16.5, with more localized expression in the stratified valve leaflets after birth. In chicken embryo aortic valves, genes characteristic of osteogenic cell lineages including periostin, osteonectin, and Id2 are expressed specifically in the collagen-rich fibrosa layer at E14. Treatment of E14 aortic valve interstitial cells (VICs) in culture with osteogenic media results in increased expression of multiple genes associated with bone formation. Treatment of VIC with Wnt3a leads to nuclear localization of beta-catenin and induction of periostin and matrix gla protein but does not induce genes associated with later stages of osteogenesis. Together, these studies provide evidence for Wnt signaling as a regulator of endocardial cushion maturation as well as valve leaflet stratification, homeostasis, and pathogenesis.

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Authors: Alfieri, C. M., Cheek, J., Chakraborty, S., & Yutzey, K. E.
Affiliations: Cincinnati Children's Hospital Medical Center (US)
Corresponding author: Yutzey, Katherine E.
ORCID: Chakraborty, Santanu
Yutzey, Katherine E.
Venue: Developmental Biology
Publisher: Elsevier BV
Published: 2010-02
Volume: 338
Issue: 2
Pages: 127-135
ISSN: 0012-1606 (ISSN-L)
DOI: 10.1016/j.ydbio.2009.11.030
PMC: PMC2814915
OpenAlex: W1968858235
Cited by: 138
References: 70
Citations by year: 2026: 2 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 11 · 2021: 4 · 2020: 9 · 2019: 10 · 2018: 10 · 2017: 10 · 2016: 18 · 2015: 9 · 2014: 12 · 2013: 7 · 2012: 7
FWCI: 2.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1262 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Developmental Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (R01 HL094319, R01 HL082716)
American Heart Association–Great Rivers Affiliate (0825627D)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: Wnt signaling, heart valve development, endocardial cushion, β-catenin, Wnt3a, Wnt2, Wnt4, Wnt9b, Wnt7b, periostin, SPARC, Id2, matrix Gla protein, valvular interstitial cells, aortic valve, chick embryo
MeSH terms: Animals, Aortic Valve, Chick Embryo, Embryo, Mammalian, Heart Valves, Osteogenesis, Proto-Oncogene Proteins, Signal Transduction, Gene Expression Regulation, Developmental, Wnt Proteins, Mice, Wnt3 Protein, Wnt3A Protein

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Wnt signaling in heart valve development and osteogenic gene induction

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