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First published online 3 August 2006
doi: 10.1242/dev.02499

Development 133, 3473-3484 (2006)
Published by The Company of Biologists 2006
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Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation

Changwon Park1,2, Kory Lavine3, Yuji Mishina4, Chu-Xia Deng5, David M. Ornitz3 and Kyunghee Choi1,2,*

1 Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA.
2 Developmental Biology Program, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA.
3 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA.
4 Molecular Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
5 Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, MD 20892, USA.

* Author for correspondence (e-mail: kchoi{at}wustl.edu)

Accepted 16 June 2006

Bone morphogenetic protein 4 (BMP4) is crucial for the formation of FLK1-expressing (FLK1+) mesodermal cells. To further define the requirement for BMP signaling in the differentiation of blood, endothelial and smooth muscle cells from FLK1+ mesoderm, we inactivated Alk3 (Bmpr1a) in FLK1+ cells by crossing Alk3floxed/floxed and Flk1+/CreAlk3+/floxed mice. Alk3 conditional knockout (CKO) mice died between E10.5 and E11.5. Unexpectedly, Alk3 CKO embryos did not show any hematopoietic defects. However, Alk3 CKO embryos displayed multiple abnormalities in vascular development, including vessel remodeling and maturation, which contributed to severe abdominal hemorrhage. Alk3 CKO embryos also displayed defects in atrioventricular canal (AVC) endocardial cushion formation in the heart. Collectively, our studies indicate a crucial role for ALK3 in vessel remodeling, vessel integrity and endocardial cushion formation during the development of the circulation system.

Key words: Hematopoiesis, Vasculogenesis, Endocardial cushion, FLK1 (KDR), ALK3 (BMPR1A), SMAD4, Mouse




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