13:50 〜 14:40
[P59-01] 神経堤細胞による冠動脈形成への寄与とレチノイン酸シグナルの早期効果
キーワード：レチノイン酸、神経堤細胞、冠動脈
Background. Retinoic acid (RA) is an important morphogen involved in cardiac development, as evidenced by the fact that a lack or excess of RA during embryonic development causes severe cardiac and great vessel anomalies. In preliminary experiments, we encountered dilatation of a coronary artery branch in the interventricular septum of RA-treated mouse embryos. The aim of the present study was to clarify the morphogenesis of the coronary artery in the RA-treated embryos destined to develop anomalies.
Methods and Results. We first examined RA-treated embryonic hearts by means of ink injection and histology. Treatment of pregnant female mice with all-trans RA at the early embryonic stage (E8.5) caused abnormalities in coronary orifice formation and branching as well as septal branch dilatation. These coronary abnormalities were reminiscent of coronary artery anomalies appeared in preotic neural crest (NC)-ablated chick embryos and Endothelin-1/endothelin receptor type-A KO mice, as previously reported, indicating the effect of RA on preotic NC cells (NCCs) migrating into the heart. To examine the distribution of NCCs, we performed lineage tracing experiments using Wnt1-Cre/R26R-lacZ mice, which demonstrated that Cre-labeled NCCs migrated into the outflow and ventricular wall were decreased and, instead, NCCs clustered between the pharyngeal arch arteries and anterior visceral endoderm in the RA-treated embryos.
Conclusions. We previously reported that NCCs from the preotic region migrate into the heart and differentiate into coronary artery smooth muscle cells. Taken together, the present results indicate that this preotic NCC population is sensitive to RA at early migrating stages, causing NC-defective coronary malformations.
Methods and Results. We first examined RA-treated embryonic hearts by means of ink injection and histology. Treatment of pregnant female mice with all-trans RA at the early embryonic stage (E8.5) caused abnormalities in coronary orifice formation and branching as well as septal branch dilatation. These coronary abnormalities were reminiscent of coronary artery anomalies appeared in preotic neural crest (NC)-ablated chick embryos and Endothelin-1/endothelin receptor type-A KO mice, as previously reported, indicating the effect of RA on preotic NC cells (NCCs) migrating into the heart. To examine the distribution of NCCs, we performed lineage tracing experiments using Wnt1-Cre/R26R-lacZ mice, which demonstrated that Cre-labeled NCCs migrated into the outflow and ventricular wall were decreased and, instead, NCCs clustered between the pharyngeal arch arteries and anterior visceral endoderm in the RA-treated embryos.
Conclusions. We previously reported that NCCs from the preotic region migrate into the heart and differentiate into coronary artery smooth muscle cells. Taken together, the present results indicate that this preotic NCC population is sensitive to RA at early migrating stages, causing NC-defective coronary malformations.