Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption.
Semaphorin 3C is a secreted member of the semaphorin gene family. To investigate its function in vivo, we have disrupted the semaphorin 3C locus in mice by targeted mutagenesis. semaphorin 3C mutant mice die within hours after birth from congenital cardiovascular defects consisting of interruption of the aortic arch and improper septation of the cardiac outflow tract. This phenotype is similar to that reported following ablation of the cardiac neural crest in chick embryos and resembles congenital heart defects seen in humans. Semaphorin 3C is expressed in the cardiac outflow tract as neural crest cells migrate into it. Their entry is disrupted in semaphorin 3C mutant mice. These data suggest that semaphorin 3C promotes crest cell migration into the proximal cardiac outflow tract.
Feiner
L
L
Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Webber
A L
AL
Brown
C B
CB
Lu
M M
MM
Jia
L
L
Feinstein
P
P
Mombaerts
P
P
Epstein
J A
JA
Raper
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D005838:Genotype; D017403:In Situ Hybridization; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D050697:Retinal Dehydrogenase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040121:Semaphorin-3A; D015398:Signal Transduction; D013997:Time Factors; D014338:Truncus Arteriosus / Q000737:chemistry*; D014764:Viral Proteins / Q000378:metabolism; D029961:Zebrafish Proteins / Q000819:agonists*
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D014764:Viral Proteins; D029961:Zebrafish Proteins; C518907:Aldh1a2 protein, zebrafish; D050697:Retinal Dehydrogenase; C045073:Cre recombinase; D019426:Integrases