Retinoic Acid and Pitx2 Regulate Early Neural Crest Survival and Migration in Craniofacial and Ocular Development
Retinoic Acid and Pitx2 Regulate Early Neural Crest Survival and Migration in Craniofacial and Ocular Development
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DOI：
10.1002/bdrb.21177
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发表时间：
2016-06-01
影响因子：
--
通讯作者：
Bohnsack, Brenda L.
中科院分区：
文献类型：
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作者：
Chawla, Bahaar;Schley, Elisa;Bohnsack, Brenda L.
先天性眼和颅面畸形与胚胎发育过程中维甲酸（RA）水平失调有关。在本研究中，我们观察到，RA和pitx2a合作调节早期颅神经嵴迁移从菱脑到咽弓和从中脑和前脑到眼周间充质和额鼻突。颅神经嵴追踪到高RA活动的区域（即，发育中的眼睛）和绕过低RA活性的区域（即，中脑）。虽然以前的研究表明，RA增加pitx2a的表达在颅神经嵴发育的后期阶段，在这些研究中，我们发现，RA抑制pitx2a的表达在早期迁移腹侧颅神经嵴。增加RA或减少Pitx2a表达降低细胞存活率和抑制腹侧神经嵴迁移。RA的减少或pitx2a的表达增加显着破坏背侧和腹侧神经嵴迁移。RA的严格控制和随后的pitx2的调节需要精确的颅神经嵴的生存和迁移。眼周间充质和额鼻突中神经嵴的这些改变可能反映了在增加的病例中观察到的颅面畸形和小眼畸形（即，如由异视黄酸暴露引起）或降低（即，如可能发生在胎儿酒精综合征）RA信号在怀孕期间
Congenital eye and craniofacial anomalies are associated with the dysregulation of retinoic acid (RA) levels during embryogenesis. In the present study, we observed that RA and pitx2a cooperatively regulate early cranial neural crest migration from the rhombencephalon to the pharyngeal arches and from the mesencephalon and prosencephalon to the periocular mesenchyme and frontonasal processes. The cranial neural crest tracked toward areas of high RA activity (i.e., developing eye) and circumvented areas of low RA activity (i.e., mesencephalon). Although previous studies have shown that RA increased pitx2a expression at later stages of cranial neural crest development, in these studies we found that RA inhibited pitx2a expression in the early migrating ventral cranial neural crest. Increased RA or decreased Pitx2a expression decreased cell survival and inhibited ventral neural crest migration. Decreased RA or increased pitx2a expression markedly disrupted both dorsal and ventral neural crest migration. The tight control of RA and subsequent regulation of pitx2 were required for precise cranial neural crest survival and migration. These alterations in the neural crest in the periocular mesenchyme and frontonasal processes may reflect the craniofacial dysmorphism and microphthalmia observed in cases of increased (i.e., as resulting from isoretinoin exposure) or decreased (i.e., as may occur in fetal alcohol syndrome) RA signaling during pregnancy