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En Face Endocardial Cushion Preparation for Planar Morphogenesis Analysis in Mouse Embryos
Published on: July 27, 2022
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Muscleblind-like 1 is required for normal heart valve development in vivo
Ryan J Coram1,2, Samantha J Stillwagon3,4, Anuradha Guggilam5
1Department of Cellular & Molecular Medicine, Lerner Research Institute, 9500 Euclid Ave. NC10, Cleveland Clinic, Cleveland, OH, 44195, USA. ryan_coram@yahoo.com.
BMC Developmental Biology
|October 17, 2015
Summary
Muscleblind-like 1 (MBNL1) is crucial for heart valve development. Its absence causes abnormal heart valve formation and function due to dysregulated TGFβ signaling and epithelial-mesenchymal transition (EMT).
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Molecular Biology
Background:
- Heart valve and septa development relies on endocardial cushion formation and remodeling.
- Epithelial-mesenchymal transition (EMT) in endocardial cushions generates mesenchyme for valve formation.
- Transforming growth factor β (TGFβ) signaling influences EMT and valve remodeling.
Purpose of the Study:
- To investigate the role of muscleblind-like 1 (MBNL1) in endocardial cushion development and valvulogenesis.
- To determine if MBNL1's function in regulating TGFβ signaling and EMT is conserved in vivo.
- To assess the impact of MBNL1 deficiency on heart valve structure and function in mice.
Main Methods:
- Utilized collagen gel invasion assays, histology, and immunohistochemistry to assess EMT and TGFβ signaling.
- Employed real-time RT-PCR for gene expression analysis.
- Applied optical coherence tomography and echocardiography to evaluate heart valve morphogenesis, ECM composition, and function.
Main Results:
- Loss of MBNL1 led to precocious TGFβ signaling and EMT in endocardial cushions.
- MBNL1-deficient mice exhibited aberrant valve morphogenesis, resulting in valve dysmorphia and regurgitation.
- Mbnl1(∆E3/∆E3) mice showed increased pigmentation, altered ECM composition, and a high incidence of septal defects.
Conclusions:
- MBNL1 plays a conserved role in negatively regulating TGFβ signaling.
- MBNL1 is essential for normal heart valve morphogenesis and in vivo homeostasis.
- Dysregulation of MBNL1 impacts cardiovascular development and function, highlighting its importance in valvulogenesis.
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