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DEVELOPMENT AND DISEASE |
1 Department of Pediatrics, Neonatal Perinatal Research Institute, Duke University Medical Center, Durham, NC 27710, USA
2 Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
3 Department of Molecular Biomedical Sciences, North Carolina State University Raleigh, NC 27606, USA
4 Institute of Molecular Embryology and Genetics, 4-24-1 Kuhonji, Kumamoto, 862-0976, Japan
*Author for correspondence (e-mail: meyer031{at}mc.duke.edu)
Accepted 1 July 2002
We present here an analysis of cardiovascular and pharyngeal arch development in mouse embryos hypomorphic for Fgf8. Previously, we have described the generation of Fgf8 compound heterozygous (Fgf8neo/–) embryos. Although early analysis demonstrated that some of these embryos have abnormal left-right (LR) axis specification and cardiac looping reversals, the number and type of cardiac defects present at term suggested an additional role for Fgf8 in cardiovascular development. Most Fgf8neo/– mutant embryos survive to term with abnormal cardiovascular patterning, including outflow tract, arch artery and intracardiac defects. In addition, these mutants have hypoplastic pharyngeal arches, small or absent thymus and abnormal craniofacial development. Neural crest cells (NCCs) populate the pharyngeal arches and contribute to many structures of the face, neck and cardiovascular system, suggesting that Fgf8 may be required for NCC development. Fgf8 is expressed within the developing pharyngeal arch ectoderm and endoderm during NCC migration through the arches. Analysis of NCC development in Fgf8neo/– mutant embryos demonstrates that NCCs are specified and migrate, but undergo cell death in areas both adjacent and distal to where Fgf8 is normally expressed. This study defines the cardiovascular defects present in Fgf8 mutants and supports a role for Fgf8 in development of all the pharyngeal arches and in NCC survival.
Key words: Fgf8, Mouse, Cardiovascular, Pharyngeal arch, DiGeorge, Neural crest, Cell death, 22q11, Double outlet right ventricle, Transposition, Arch artery, Patterning.
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