PDF(Pubmed)
Abstract：
BACKGROUND: During embryogenesis, cardiac neural crest-derived cells (NCs) migrate into the pharyngeal arches and give rise to the vascular smooth muscle cells (vSMCs) of the pharyngeal arch arteries (PAAs). vSMCs are critical for the remodeling of the PAAs into their final adult configuration, giving rise to the aortic arch and its arteries (AAAs).
RESULTS: We investigated the role of SMAD4 in NC-to-vSMC differentiation using lineage-specific inducible mouse strains. We found that the expression of SMAD4 in the NC is indelible for regulating the survival of cardiac NCs. Although the ablation of SMAD4 at E9.5 in the NC lineage led to a near-complete absence of NCs in the pharyngeal arches, PAAs became invested with vSMCs derived from a compensatory source. Analysis of AAA development at E16.5 showed that the alternative vSMC source compensated for the lack of NC-derived vSMCs and rescued AAA morphogenesis.
CONCLUSIONS: Our studies uncovered the requisite role of SMAD4 in the contribution of the NC to the pharyngeal arch mesenchyme. We found that in the absence of SMAD4+ NCs, vSMCs around the PAAs arose from a different progenitor source, rescuing AAA morphogenesis. These findings shed light on the remarkable plasticity of developmental mechanisms governing AAA development.
RESULTS: We investigated the role of SMAD4 in NC-to-vSMC differentiation using lineage-specific inducible mouse strains. We found that the expression of SMAD4 in the NC is indelible for regulating the survival of cardiac NCs. Although the ablation of SMAD4 at E9.5 in the NC lineage led to a near-complete absence of NCs in the pharyngeal arches, PAAs became invested with vSMCs derived from a compensatory source. Analysis of AAA development at E16.5 showed that the alternative vSMC source compensated for the lack of NC-derived vSMCs and rescued AAA morphogenesis.
CONCLUSIONS: Our studies uncovered the requisite role of SMAD4 in the contribution of the NC to the pharyngeal arch mesenchyme. We found that in the absence of SMAD4+ NCs, vSMCs around the PAAs arose from a different progenitor source, rescuing AAA morphogenesis. These findings shed light on the remarkable plasticity of developmental mechanisms governing AAA development.
摘要：
背景：在胚胎发生过程中，心脏神经c衍生细胞（NC）迁移到咽弓并产生咽弓动脉（PAA）的血管平滑肌细胞（vSMC）。vSMC对于将PAA重塑为最终的成人配置至关重要，引起主动脉弓及其动脉（AAAs）。
结果：我们使用谱系特异性诱导型小鼠品系研究了SMAD4在NC到vSMC分化中的作用。我们发现SMAD4在NC中的表达对于调节心脏NC的存活是不可磨灭的。尽管在NC谱系中E9.5处消融SMAD4导致咽弓中几乎完全没有NC，PAA投资于来自补偿性来源的vSMC。在E16.5对AAA发育的分析表明，替代的vSMC来源弥补了NC衍生的vSMC的缺乏，并挽救了AAA形态发生。
结论：我们的研究揭示了SMAD4在NC对咽弓间质的贡献中的必要作用。我们发现，在没有SMAD4+NC的情况下，PAA周围的vSMC来自不同的祖先来源，拯救AAA形态发生。这些发现揭示了控制AAA发展的发展机制的显着可塑性。
结果：我们使用谱系特异性诱导型小鼠品系研究了SMAD4在NC到vSMC分化中的作用。我们发现SMAD4在NC中的表达对于调节心脏NC的存活是不可磨灭的。尽管在NC谱系中E9.5处消融SMAD4导致咽弓中几乎完全没有NC，PAA投资于来自补偿性来源的vSMC。在E16.5对AAA发育的分析表明，替代的vSMC来源弥补了NC衍生的vSMC的缺乏，并挽救了AAA形态发生。
结论：我们的研究揭示了SMAD4在NC对咽弓间质的贡献中的必要作用。我们发现，在没有SMAD4+NC的情况下，PAA周围的vSMC来自不同的祖先来源，拯救AAA形态发生。这些发现揭示了控制AAA发展的发展机制的显着可塑性。
