Schuh T J, Kimelman D
Department of Biochemistry, University of Washington, Seattle 98195, USA.
Mech Dev. 1995 May;51(1):39-49. doi: 10.1016/0925-4773(94)00346-o.
Isomers of retinoic acid are considered likely regulators of developmental pattern formation in vertebrate embryos. The orphan receptor COUP-TFI, which can alter cellular responses to retinoic acid in cultured cells, is expressed in distinct regions of the developing zebrafish and mouse anterior central nervous system. We asked if COUP-TFI can modulate retinoic acid signaling and anterior neural development in a vertebrate embryo by examining: (1) whether COUP-TFI could alter transcriptional responses to retinoic acid in Xenopus embryonic explants, and (2) whether misexpression of COUP-TFI could regulate anterior neural gene expression during early Xenopus development. The results from these studies show that COUP-TFI is a potent regulator of retinoic acid-induced gene expression in Xenopus embryonic cells, and that misexpression of COUP-TFI causes deficiencies in anterior neural structures and head development in Xenopus embryos with a concomitant change in anterior neural gene expression. These results support the proposition that COUP-TFI has a role in the elaboration and patterning of anterior neural gene expression in vertebrates, possibly via effects on the retinoic acid signaling pathways.
维甲酸异构体被认为是脊椎动物胚胎发育模式形成的潜在调节因子。孤儿受体COUP-TFI能够改变培养细胞对维甲酸的细胞反应,在发育中的斑马鱼和小鼠前中枢神经系统的不同区域表达。我们通过以下研究来探究COUP-TFI是否能调节脊椎动物胚胎中的维甲酸信号传导和前神经发育:(1)COUP-TFI是否能改变非洲爪蟾胚胎外植体对维甲酸的转录反应,以及(2)COUP-TFI的错误表达是否能在非洲爪蟾早期发育过程中调节前神经基因的表达。这些研究结果表明,COUP-TFI是非洲爪蟾胚胎细胞中维甲酸诱导基因表达的有效调节因子,并且COUP-TFI的错误表达会导致非洲爪蟾胚胎前神经结构和头部发育缺陷,同时前神经基因表达也会发生变化。这些结果支持了这样一种观点,即COUP-TFI可能通过影响维甲酸信号通路,在脊椎动物前神经基因表达的细化和模式形成中发挥作用。