Tbx20 acts upstream of Wnt signaling to regulate endocardial cushion formation and valve remodeling during mouse cardiogenesis

Xiaoqiang Cai, Weijia Zhang, Jun Hu, Lu Zhang, Nishat Sultana, Bingruo Wu, Weibin Cai, Bin Zhou, Chen Leng Cai

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Cardiac valves are essential to direct forward blood flow through the cardiac chambers efficiently. Congenital valvular defects are prevalent among newborns and can cause an immediate threat to survival as well as long-term morbidity. Valve leaflet formation is a rigorously programmed process consisting of endocardial epithelial-mesenchymal transformation (EMT), mesenchymal cell proliferation, valve elongation and remodeling. Currently, little is known about the coordination of the diverse signals that regulate endocardial cushion development and valve elongation. Here, we report that the T-box transcription factor Tbx20 is expressed in the developing endocardial cushions and valves throughout heart development. Ablation of Tbx20 in endocardial cells causes severe valve elongation defects and impaired cardiac function in mice. Our study reveals that endocardial Tbx20 is crucial for valve endocardial cell proliferation and extracellular matrix development, but is not required for initiation of EMT. Elimination of Tbx20 also causes aberrant Wnt/ß-catenin signaling in the endocardial cushions. In addition, Tbx20 regulates Lef1, a key transcriptional mediator for Wnt/ß-catenin signaling, in this developmental process. Our study suggests a model in which Tbx20 regulates the Wnt pathway to direct endocardial cushion maturation and valve elongation, and provides new insights into the etiology of valve defects in humans.

Original languageEnglish (US)
Pages (from-to)3176-3187
Number of pages12
JournalDevelopment (Cambridge)
Volume140
Issue number15
DOIs
StatePublished - Aug 1 2013

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Endocardial Cushions
Catenins
Epithelial-Mesenchymal Transition
Heart Valves
Cell Proliferation
Wnt Signaling Pathway
Extracellular Matrix
Transcription Factors
Morbidity
Survival

Keywords

  • Cardiac valve
  • Heart development
  • Mouse
  • Tbx20

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Tbx20 acts upstream of Wnt signaling to regulate endocardial cushion formation and valve remodeling during mouse cardiogenesis. / Cai, Xiaoqiang; Zhang, Weijia; Hu, Jun; Zhang, Lu; Sultana, Nishat; Wu, Bingruo; Cai, Weibin; Zhou, Bin; Cai, Chen Leng.

In: Development (Cambridge), Vol. 140, No. 15, 01.08.2013, p. 3176-3187.

Research output: Contribution to journalArticle

Cai, Xiaoqiang ; Zhang, Weijia ; Hu, Jun ; Zhang, Lu ; Sultana, Nishat ; Wu, Bingruo ; Cai, Weibin ; Zhou, Bin ; Cai, Chen Leng. / Tbx20 acts upstream of Wnt signaling to regulate endocardial cushion formation and valve remodeling during mouse cardiogenesis. In: Development (Cambridge). 2013 ; Vol. 140, No. 15. pp. 3176-3187.
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