Fate of the mammalian cardiac neural crest

A subpopulation of neural crest termed the cardiac neural crest is required in avian embryos to initiate reorganization of the outflow tract of the de veloping cardiovascular system. In mammalian embryos, it has not been previ ously experimentally possible to study the long-term fate of this populatio n, although there is strong inference that a similar population exists and is perturbed in a number of genetic and teratogenic contexts. We have emplo yed a two-component genetic system based on Cre/lox recombination to label indelibly the entire mouse neural crest population at the time of its forma tion, and to detect it at any time thereafter. Labeled cells are detected t hroughout gestation and in postnatal stages in major tissues that are known or predicted to be derived from neural crest. Labeling is highly specific and highly efficient. In the region of the heart, neural-crest-derived cell s surround the pharyngeal arch arteries from the time of their formation an d undergo an altered distribution coincident with the reorganization of the se vessels. Labeled cells populate the aorticopulmonary septum and conotrun cal cushions prior to and during overt septation of the outflow tract, and surround the thymus and thyroid as these organs form. Neural-crest-derived mesenchymal cells are abundantly distributed in midgestation (E9.5-12.5), a nd adult derivatives of the third, fourth and sixth pharyngeal arch arterie s retain a substantial contribution of labeled cells. However, the populati on of neural-crest-derived cells that infiltrates the conotruncus and which surrounds the noncardiac pharyngeal organs is either overgrown or selectiv ely eliminated as development proceeds, resulting for these tissues in a mo dest to marginal contribution in late fetal and postnatal life.