PlexinA2 and semaphorin signaling during cardiac neural crest development.
Classic studies using avian model systems have demonstrated that cardiac neural crest cells are required for proper development of the cardiovascular system. Environmental influences that perturb neural crest development cause congenital heart defects in laboratory animals and in man. However, little progress has been made in determining molecular programs specifically regulating cardiac neural crest migration and function. Only recently have complex transgenic tools become available that confirm the presence of cardiac neural crest cells in the mammalian heart. These studies have relied upon the use of transgenic mouse lines and fate-mapping studies using Cre recombinase and neural crest-specific promoters. In this study, we use these techniques to demonstrate that PlexinA2 is expressed by migrating and postmigratory cardiac neural crest cells in the mouse. Plexins function as co-receptors for semaphorin signaling molecules and mediate axon pathfinding in the central nervous system. We demonstrate that PlexinA2-expressing cardiac neural crest cells are patterned abnormally in several mutant mouse lines with congenital heart disease including those lacking the secreted signaling molecule Semaphorin 3C. These data suggest a parallel between the function of semaphorin signaling in the central nervous system and in the patterning of cardiac neural crest in the periphery.
Brown
C B
CB
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Feiner
L
L
Lu
M M
MM
Li
J
J
Ma
X
X
Webber
A L
AL
Jia
L
L
Raper
J A
JA
Epstein
J A
JA
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D005697:Galactosides / Q000378:metabolism; D017403:In Situ Hybridization; D007211:Indoles / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D039942:Neuropilin-1; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology*; D040121:Semaphorin-3A; D013997:Time Factors; D014764:Viral Proteins / Q000378:metabolism
D002352:Carrier Proteins; D005697:Galactosides; D007211:Indoles; D009419:Nerve Tissue Proteins; C492113:Plxna2 protein, mouse; D011956:Receptors, Cell Surface; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D014764:Viral Proteins; D039942:Neuropilin-1; C045073:Cre recombinase; D019426:Integrases; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside