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Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium.
- Source :
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BMC developmental biology [BMC Dev Biol] 2008 Jul 30; Vol. 8, pp. 75. Date of Electronic Publication: 2008 Jul 30. - Publication Year :
- 2008
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Abstract
- Background: Msx1 and Msx2, which belong to the highly conserved Nk family of homeobox genes, display overlapping expression patterns and redundant functions in multiple tissues and organs during vertebrate development. Msx1 and Msx2 have well-documented roles in mediating epithelial-mesenchymal interactions during organogenesis. Given that both Msx1 and Msx2 are crucial downstream effectors of Bmp signaling, we investigated whether Msx1 and Msx2 are required for the Bmp-induced endothelial-mesenchymal transformation (EMT) during atrioventricular (AV) valve formation.<br />Results: While both Msx1-/- and Msx2-/- single homozygous mutant mice exhibited normal valve formation, we observed hypoplastic AV cushions and malformed AV valves in Msx1-/-; Msx2-/- mutants, indicating redundant functions of Msx1 and Msx2 during AV valve morphogenesis. In Msx1/2 null mutant AV cushions, we found decreased Bmp2/4 and Notch1 signaling as well as reduced expression of Has2, NFATc1 and Notch1, demonstrating impaired endocardial activation and EMT. Moreover, perturbed expression of chamber-specific genes Anf, Tbx2, Hand1 and Hand2 reveals mispatterning of the Msx1/2 double mutant myocardium and suggests functions of Msx1 and Msx2 in regulating myocardial signals required for remodelling AV valves and maintaining an undifferentiated state of the AV myocardium.<br />Conclusion: Our findings demonstrate redundant roles of Msx1 and Msx2 in regulating signals required for development of the AV myocardium and formation of the AV valves.
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Body Patterning
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins genetics
Embryo, Mammalian cytology
Embryo, Mammalian embryology
Endocardial Cushions cytology
Endocardium cytology
Endocardium embryology
Gene Expression
Gene Expression Regulation, Developmental
Heart Valves cytology
Heart Valves embryology
Mesoderm cytology
Mesoderm embryology
Mice
Mice, Inbred BALB C
NFATC Transcription Factors genetics
Organogenesis
Receptor, Notch1 genetics
Transforming Growth Factor beta genetics
Endocardial Cushions embryology
Homeodomain Proteins genetics
MSX1 Transcription Factor genetics
Myocardium cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-213X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- BMC developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 18667074
- Full Text :
- https://doi.org/10.1186/1471-213X-8-75