Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse.
Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse.
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DOI：
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发表时间：
2002-10
期刊：
影响因子：
4.6
通讯作者：
R. Abu‐Issa;Graham Smyth;I. Smoak;K. Yamamura;E. Meyers
中科院分区：
文献类型：
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作者：
R. Abu‐Issa;Graham Smyth;I. Smoak;K. Yamamura;E. Meyers
我们在此分析了Fgf8亚型小鼠胚胎的心血管和咽弓发育。在此之前，我们已经描述了Fgf8复合杂合胚胎（Fgf8(neo/-)）的产生。尽管早期的分析表明，这些胚胎中的一些具有异常的左右（LR）轴特征和心环逆转，但足月时出现的心脏缺陷的数量和类型表明Fgf8在心血管发育中的额外作用。大多数Fgf8（neo/-）突变胚胎存活至足月，伴有异常的心血管模式，包括流出道、弓动脉和心内缺陷。此外，这些突变体的咽弓发育不全，胸腺小或缺失，颅面发育异常。神经嵴细胞（Neural crest cells, NCCs）分布于咽弓，并参与面部、颈部和心血管系统的许多结构，这表明Fgf8可能是NCC发育所必需的。在NCC通过咽弓迁移过程中，Fgf8在发育中的咽弓外胚层和内胚层表达。对Fgf8（neo/-）突变胚胎中NCC发育的分析表明，NCC是特定的和迁移的，但在Fgf8正常表达的邻近和远端区域都会发生细胞死亡。本研究确定了Fgf8突变体中存在的心血管缺陷，并支持Fgf8在所有咽弓的发展和NCC存活中的作用。
We present here an analysis of cardiovascular and pharyngeal arch development in mouse embryos hypomorphic for Fgf8. Previously, we have described the generation of Fgf8 compound heterozygous (Fgf8(neo/-)) embryos. Although early analysis demonstrated that some of these embryos have abnormal left-right (LR) axis specification and cardiac looping reversals, the number and type of cardiac defects present at term suggested an additional role for Fgf8 in cardiovascular development. Most Fgf8(neo/-) mutant embryos survive to term with abnormal cardiovascular patterning, including outflow tract, arch artery and intracardiac defects. In addition, these mutants have hypoplastic pharyngeal arches, small or absent thymus and abnormal craniofacial development. Neural crest cells (NCCs) populate the pharyngeal arches and contribute to many structures of the face, neck and cardiovascular system, suggesting that Fgf8 may be required for NCC development. Fgf8 is expressed within the developing pharyngeal arch ectoderm and endoderm during NCC migration through the arches. Analysis of NCC development in Fgf8(neo/-) mutant embryos demonstrates that NCCs are specified and migrate, but undergo cell death in areas both adjacent and distal to where Fgf8 is normally expressed. This study defines the cardiovascular defects present in Fgf8 mutants and supports a role for Fgf8 in development of all the pharyngeal arches and in NCC survival.