CYP26A1 and CYP26C1 cooperatively regulate anterior-posterior patterning of the developing brain and the production of migratory cranial neural crest cells in the mouse.
CYP26A1 and CYP26C1 cooperatively regulate anterior-posterior patterning of the developing brain and the production of migratory cranial neural crest cells in the mouse.
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DOI：
10.1016/j.ydbio.2006.09.045
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发表时间：
2007-02
影响因子：
2.7
通讯作者：
Masayuki Uehara;K. Yashiro;S. Mamiya;J. Nishino;P. Chambon;P. Dollé;Y. Sakai
中科院分区：
文献类型：
--
作者：
Masayuki Uehara;K. Yashiro;S. Mamiya;J. Nishino;P. Chambon;P. Dollé;Y. Sakai
视黄酸信号的适当调节对于脊椎动物中枢神经系统沿着前后（A-P）轴的模式化是必不可少的。虽然CYP 26 A1和CYP 26 C1，视黄酸降解酶，在原肠胚的前端表达，已被认为在中枢神经系统模式中发挥重要作用，其贡献的详细机制仍然在很大程度上未知。我们现在已经通过产生敲除小鼠分析了CYP 26 A1和CYP 26 C1的功能。CYP 26 C1的缺失似乎不影响胚胎发育，表明CYP 26 A1和CYP 26 C1在功能上是冗余的。相比之下，发现缺乏CYP 26 A1和CYP 26 C1的小鼠表现出与A-P图案缺陷相关的明显的大脑前部截短，这反映了以前部身份为代价的后部身份的扩展。此外，Cyp 26 a1 −/− Cyp 26 c1 −/−小鼠不能在前脑和中脑产生迁移的颅神经嵴细胞。这些观察结果，以及Cyp 26 a1突变小鼠的重新评估，表明CYP 26 A1和CYP 26 C1的活性是正确的A-P模式和生产的迁移性颅神经嵴细胞在发育中的哺乳动物大脑所必需的。
The appropriate regulation of retinoic acid signaling is indispensable for patterning of the vertebrate central nervous system along the anteroposterior (A–P) axis. Although both CYP26A1 and CYP26C1, retinoic acid-degrading enzymes that are expressed at the anterior end of the gastrulating mouse embryo, have been thought to play an important role in central nervous system patterning, the detailed mechanism of their contribution has remained largely unknown. We have now analyzed CYP26A1 and CYP26C1 function by generating knockout mice. Loss of CYP26C1 did not appear to affect embryonic development, suggesting that CYP26A1 and CYP26C1 are functionally redundant. In contrast, mice lacking both CYP26A1 and CYP26C1 were found to manifest a pronounced anterior truncation of the brain associated with A–P patterning defects that reflect expansion of posterior identity at the expense of anterior identity. Furthermore, Cyp26a1−/−Cyp26c1−/−mice fail to produce migratory cranial neural crest cells in the forebrain and midbrain. These observations, together with a reevaluation of Cyp26a1 mutant mice, suggest that the activity of CYP26A1 and CYP26C1 is required for correct A–P patterning and production of migratory cranial neural crest cells in the developing mammalian brain.