Cardiac neural crest of the mouse embryo:: axial level of origin, migratory pathway and cell autonomy of the splotch (Sp2H) mutant effect
Cardiac neural crest of the mouse embryo:: axial level of origin, migratory pathway and cell autonomy of the splotch (Sp2H) mutant effect
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DOI：
10.1242/dev.01197
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发表时间：
2004-07-01
期刊：
影响因子：
4.6
通讯作者：
Copp, AJ
中科院分区：
文献类型：
--
作者：
Chan, WY;Cheung, CS;Copp, AJ
神经嵴的一个亚群在心脏流出道的发育中起着至关重要的作用。对鸟类的研究已经绘制出了“心脏”神经嵴细胞从神经管到发育中的心脏的完整迁移路径。心脏神经嵴谱系也已知存在于哺乳动物中，尽管缺乏关于其轴向起源水平和迁移模式的详细信息。我们采用局灶细胞标记和原位移植，然后进行全胚培养，以确定小鼠胚胎心脏神经嵴的时空迁移模式。产后后脑和4号体之间的轴向水平为心脏提供神经嵴细胞，2号体对面的神经管是最丰富的来源。心脏神经嵴从神经管向外迁移始于7体体期，细胞沿体体背外侧、体体内侧和体体之间的途径迁移。随后，心脏神经嵴细胞穿过主动脉周围间质，沿咽外侧，穿过咽弓3、4和6，进入主动脉囊。流出道间质的定植在32岁时被检测到。纯合子胚胎;Sp（2H）突变显示心脏神经嵴迁移延迟发生，尽管随后的迁移途径与野生型相似。Sp(2H)/Sp（2H）胚胎沿心脏迁移途径的神经嵴细胞数量显著减少。为了解决目前关于斑点型心脏神经嵴缺损细胞自主性的争议，我们在野生型和斑点型胚胎之间进行了预迁移神经嵴的相互移植。Sp(2H)/Sp（2H）细胞在+/+环境下正常迁移，+/+细胞在Sp(2H)/Sp（2H）环境下正常迁移。相反，将Sp(2H)/+或Sp(2H)/Sp（2H）神经嵴细胞移植到Sp(2H)/Sp（2H）环境中，沿心脏途径的迁移均发生阻滞。我们得出结论，斑点突变胚胎心脏神经嵴迁移迟缓与神经嵴细胞及其迁移环境的遗传缺陷有关。
A sub-population of the neural crest is known to play a crucial role in development of the cardiac outflow tract. Studies in avians have mapped the complete migratory pathways taken by 'cardiac' neural crest cells en route from the neural tube to the developing heart. A cardiac neural crest lineage is also known to exist in mammals, although detailed information on its axial level of origin and migratory pattern are lacking. We used focal cell labelling and orthotopic grafting, followed by whole embryo culture, to determine the spatio-temporal migratory pattern of cardiac neural crest in mouse embryos. Axial levels between the post-otic hindbrain and somite 4 contributed neural crest cells to the heart, with the neural tube opposite somite 2 being the most prolific source. Emigration of cardiac neural crest from the neural tube began at the 7-somite stage, with cells migrating in pathways dorsolateral to the somite, medial to the somite, and between somites. Subsequently, cardiac neural crest cells migrated through the peri-aortic mesenchyme, lateral to the pharynx, through pharyngeal arches 3, 4 and 6, and into the aortic sac. Colonisation of the outflow tract mesenchyme was detected at the 32-somite stage. Embryos homozygous; for the Sp(2H) mutation show delayed onset of cardiac neural crest emigration, although the pathways of subsequent migration resembled wild type. The number of neural crest cells along the cardiac migratory pathway was significantly reduced in Sp(2H)/Sp(2H) embryos. To resolve current controversy over the cell autonomy of the splotch cardiac neural crest defect, we performed reciprocal grafts of premigratory neural crest between wild type and splotch embryos. Sp(2H)/Sp(2H) cells migrated normally in the +/+ environment, and +/+ cells migrated normally in the Sp(2H)/Sp(2H) environment. In contrast, retarded migration along the cardiac route occurred when either Sp(2H)/+ or Sp(2H)/Sp(2H) neural crest cells were grafted into the Sp(2H)/Sp(2H) environment. We conclude that the retardation of cardiac neural crest migration in splotch mutant embryos requires the genetic defect in both neural crest cells and their migratory environment.