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A constitutive mutation of ALK5 disrupts cardiac looping and morphogenesis in mice
- Source :
- Developmental Biology. July 1, 1998, Vol. 199 Issue 1, p72, 8 p.
- Publication Year :
- 1998
-
Abstract
- TGF[Beta] family members are implicated in cardiac organogenesis, growth control, and positional information, including the direction of cardiac looping. However, genetic analysis of TGF[Beta] signaling in mice has been confounded, in some cases, by noncardiac and generalized defects. Hence, deciphering TGF[Beta] function in myocardium would benefit from cardiac-restricted mutations. We developed a constitutively activated type I receptor, [ALK5.sup.L193A,P194A,T204D], and directed it to embryonic myocardium in transgenic mice. Expression of the activated ALK5 gene arrests looping morphogenesis and causes a linear, dilated, hypoplastic heart tube, despite normal expression of Nkx2.5 and dHAND, cardiogenic transcription factors whose absence provokes a similar phenotype. Ventricular hypoplasia was associated with precocious induction of the cyclin-dependent kinase inhibitor, p21. Thus, an ALK5-sensitive pathway mediates looping, perhaps through control of cardiac myocyte proliferation. Key Words: ALK5; cardiac development; looping; p21; TGF[Beta].
Details
- ISSN :
- 00121606
- Volume :
- 199
- Issue :
- 1
- Database :
- Gale General OneFile
- Journal :
- Developmental Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.21067779