Cardiac neural crest cells are multipotent migratory cells that contribute to the formation of the cardiac outflow tract and pharyngeal arch arteries. Neural crest-related developmental defects account for a large proportion of congenital heart disorders. Recently, the genetic bases for some of these disorders have been elucidated, and signaling pathways required for induction,migration and differentiation of cardiac neural crest have emerged. Bone morphogenetic proteins comprise a family of secreted ligands implicated in numerous aspects of organogenesis, including heart and neural crest development. However, it has remained generally unclear whether BMP ligands act directly on neural crest or cardiac myocytes during cardiac morphogenesis,or function indirectly by activating other cell types. Studies on BMP receptor signaling during organogenesis have been hampered by the fact that receptor knockouts often lead to early embryonic lethality. We have used a Cre/loxP system for neural crest-specific deletion of the type I receptor, ALK2, in mouse embryos. Mutant mice display cardiovascular defects, including persistent truncus arteriosus, and abnormal maturation of the aortic arch reminiscent of common forms of human congenital heart disease. Migration of mutant neural crest cells to the outflow tract is impaired, and differentiation to smooth muscle around aortic arch arteries is deficient. Moreover, in Alk2 mutants, the distal outflow tract fails to express Msx1, one of the major effectors of BMP signaling. Thus, the type I BMP receptor ALK2 plays an essential cell-autonomous role in the development of the cardiac outflow tract and aortic arch derivatives.
Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells
Vesa Kaartinen, Marek Dudas, Andre Nagy, Somyoth Sridurongrit, Min Min Lu, Jonathan A. Epstein; Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells. Development 15 July 2004; 131 (14): 3481–3490. doi: https://doi.org/10.1242/dev.01214
Download citation file:
Sign in
Client Account
Sign in via your institution
Sign in via ShibbolethAdvertisement
About us

Our publisher, The Company of Biologists, turns 100 this year. Read about the history of the Company and find out what Sarah Bray, our Chair of the Board of Directors, has to say.
Biologists @ 100 - join us in Liverpool in March 2025

We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register by 28 February 2025 to join us in March 2025 in Liverpool, UK.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues

Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology

In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
In preprints
Did you know that Development publishes perspectives on recent preprints? These articles help our readers navigate the ever-growing preprint literature. We welcome proposals for ‘In preprints’ articles, so please do get in touch if you’d like to contribute.