Fate of the mammalian cardiac neural crest

TLDR

Cardiac neural crest cells are essential for outflow tract remodeling in avian embryos, yet their long‑term fate in mammals has remained experimentally elusive despite strong evidence of a similar population involved in genetic and teratogenic defects. A Cre/lox–based genetic system was used to permanently label the entire mouse neural crest at its formation, enabling tracking at all subsequent stages. Indelible labeling revealed that cardiac neural crest cells persist throughout gestation and into adulthood, contributing extensively to the aorticopulmonary septum, conotruncal cushions, thymus, thyroid, and pharyngeal arch arteries, while their presence in the conotruncus and noncardiac pharyngeal organs diminishes over time, resulting in only modest contributions in late fetal and postnatal stages.

Abstract

ABSTRACT A subpopulation of neural crest termed the cardiac neural crest is required in avian embryos to initiate reorganization of the outflow tract of the developing cardiovascular system. In mammalian embryos, it has not been previously experimentally possible to study the long-term fate of this population, although there is strong inference that a similar population exists and is perturbed in a number of genetic and teratogenic contexts. We have employed a two-component genetic system based on Cre/lox recombination to label indelibly the entire mouse neural crest population at the time of its formation, and to detect it at any time thereafter. Labeled cells are detected throughout 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 cells surround the pharyngeal arch arteries from the time of their formation and undergo an altered distribution coincident with the reorganization of these vessels. Labeled cells populate the aorticopulmonary septum and conotruncal 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), and adult derivatives of the third, fourth and sixth pharyngeal arch arteries retain a substantial contribution of labeled cells. However, the population of neural-crest-derived cells that infiltrates the conotruncus and which surrounds the noncardiac pharyngeal organs is either overgrown or selectively eliminated as development proceeds, resulting for these tissues in a modest to marginal contribution in late fetal and postnatal life.