Normal fate and altered function of the cardiac neural crest cell lineage in retinoic acid receptor mutant embryos.
Mouse embryos lacking the retinoic acid (RA) receptors RARalpha1 and RARbeta suffer from a failure to properly septate (divide) the early outflow tract of the heart into distinct aortic and pulmonary channels, a phenotype termed persistent truncus arteriosus. This phenotype is associated with a failure in the development of the cardiac neural crest cell lineage, which normally forms the aorticopulmonary septum. In this study, we examined the fate of the neural crest lineage in RARalpha1/RARbeta mutant embryos by crossing with the Wnt1-cre and conditional R26R alleles, which together constitute a genetic lineage marker for the neural crest. We find that the number, migration, and terminal fate of the cardiac neural crest is normal in mutant embryos; however, the specific function of these cells in forming the aorticopulmonary septum is impaired. We furthermore show that the neural crest cells themselves do not utilize retinoid receptors and do not respond to RA during this process, but rather that the phenotype is cell non-autonomous for the neural crest cell lineage. This suggests that an alternative tissue in the vicinity of the outflow tract of the heart responds directly to RA, and thereby induces or permits the neural crest cell lineage to initiate aorticopulmonary septation.
Institute for Genetic Medicine, University of Southern California Keck School of Medicine, 2250 Alcazar St, IGM240, Los Angeles, CA 90033, USA.
Xiaobing
X
Jiang
Bibha
B
Choudhary
Esther
E
Merki
Kenneth R
KR
Chien
Robert E
RE
Maxson
Henry M
HM
Sucov
D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D005318:Fetal Heart / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D010641:Phenotype; D018168:Receptors, Retinoic Acid / Q000172:deficiency / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D014339:Truncus Arteriosus, Persistent / Q000196:embryology / Q000235:genetics / Q000378:metabolism
C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082925:retinoic acid receptor beta