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Over-expression of Fgf8 in cardiac neural crest cells leads to persistent truncus arteriosus.

Authors :
Tian, Aijuan
Wang, Shangqi
Wang, Haoru
Li, Nan
Liu, Han
Zhou, Hailing
Chen, Xiaoyan
Liu, Xuena
Deng, Jiamin
Xiao, Jing
Liu, Chao
Source :
Journal of Molecular Histology; Apr2021, Vol. 52 Issue 2, p351-361, 11p
Publication Year :
2021

Abstract

During cardiogenesis, the outflow tract undergoes a complicated morphogenesis, including the re-alignment of the great blood vessels, and the separation of aorta and pulmonary trunk. The deficiency of FGF8 in the morphogenesis of outflow tract has been well studied, however, the effect of over-dosed FGF8 on the development of outflow tract remains unknown. In this study, Rosa26R-Fgf8 knock-in allele was constitutively activated by Wnt1-cre transgene in the mouse neural crest cells presumptive for the endocardial cushion of outflow tract. Surprisingly, Wnt1-cre; Rosa26R-Fgf8 mouse embryos exhibited persistent truncus arteriosus and died prior to E15.5. The cardiac neural crest cells in Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus did not degenerate as in WT controls, but proliferated into a thickened endocardial cushion and then, blocked the blood outflow from cardiac chambers into the lungs, which resulted in the embryonic lethality. Although the spiral aorticopulmonary septum failed to form, the differentiaion of the endothelium and smooth muscle in the Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus were impacted little. However, lineage tracing assay showed that the neural crest derived cells aggregated in the cushion layer, but failed to differentiate into the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Further investigation displayed the reduced p-Akt and p-Erk immunostaining, and the decreased Bmp2 and Bmp4 transcription in the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Our findings suggested that Fgf8 over-expression in cardiac neural crest impaired the formation of aorticopulmonary septum by suppressing the endothelial differentiation and stimulating the proliferation of endocardial cushion cells, which implicated a novel etiology of persistent truncus arteriosus. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15672379
Volume :
52
Issue :
2
Database :
Complementary Index
Journal :
Journal of Molecular Histology
Publication Type :
Academic Journal
Accession number :
149572710
Full Text :
https://doi.org/10.1007/s10735-021-09956-2