Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse.
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 (Fgf8(neo/-)) 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 Fgf8(neo/-) 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 Fgf8(neo/-) 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.
Abu-Issa
Radwan
R
Department of Pediatrics, Neonatal Perinatal Research Institute, Duke University Medical Center, Durham, NC 27710, USA.
Smyth
Graham
G
Smoak
Ida
I
Yamamura
Ken-ichi
K
Meyers
Erik N
EN
D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D019521:Body Patterning; D001934:Branchial Region / Q000002:abnormalities / Q000196:embryology*; D018376:Cardiovascular Abnormalities / Q000378:metabolism*; D002319:Cardiovascular System / Q000196:embryology; D002452:Cell Count; D002455:Cell Division; D002465:Cell Movement; D003331:Coronary Vessels / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006321:Heart / Q000196:embryology; D006330:Heart Defects, Congenital / Q000196:embryology / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011651:Pulmonary Artery / Q000002:abnormalities / Q000196:embryology; D018168:Receptors, Retinoic Acid / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D018168:Receptors, Retinoic Acid; D020825:T-Box Domain Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D029961:Zebrafish Proteins; C496457:Fgf8 protein, mouse; C498766:Hand2 protein, mouse; C491573:Tbx1 protein, mouse; C410915:hand2 protein, zebrafish; C082927:retinoic acid binding protein I, cellular