Investigation of retinoic acid function during embryonic brain development using retinaldehyde-rescued Rdh10 knockout mice
Investigation of retinoic acid function during embryonic brain development using retinaldehyde-rescued Rdh10 knockout mice
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DOI：
10.1002/dvdy.23999
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发表时间：
2013-09-01
影响因子：
2.5
通讯作者：
Duester, Gregg
中科院分区：
文献类型：
--
作者：
Chatzi, Christina;Cunningham, Thomas J.;Duester, Gregg
背景：视黄酸（RA）信号控制后脑内的模式和神经元分化，但前脑RA功能仍有争议。RA是由视黄醇脱氢酶（retinol dehydrogenase， RDH）将视黄醇代谢为视黄醛，再由视黄醇脱氢酶（retinaldehyde dehydrogenase， RALDH）将视黄醛代谢为RA产生的。先前对Raldh2-/-和Raldh3-/-小鼠的研究表明，前脑基底节区γ -氨基丁酸（GABA）能和多巴胺能分化需要RA，但在早期前脑模式或随后的前脑皮质扩张中没有观察到RA的需要。然而，其他研究表明RA控制前脑模式，对乙基亚硝基源诱导的Rdh10突变体的分析表明，脑膜中合成的RA刺激前脑皮质扩张。结果：我们产生了在头部早期和脑膜后期缺乏RA活性的Rdh10-/-小鼠胚胎。我们观察到后脑模式和眼RA信号的缺陷，但早期前脑模式未受影响。视黄醛处理E7-E9的Rdh10-/-胚胎可修复颅骨骨骼缺陷，导致E14.5胚胎缺乏脑膜RA活性，但保持正常的前脑形状和皮质扩张。结论：Rdh10-/-胚胎表明RA控制后脑而不是早期前脑模式，而对视黄醛拯救的Rdh10-/-胚胎的研究表明脑膜RA合成对刺激前脑皮质扩张是不必要的。科学通报，2013(2):1 - 4。(C) 2013 Wiley期刊公司
Background: Retinoic acid (RA) signaling controls patterning and neuronal differentiation within the hindbrain, but forebrain RA function remains controversial. RA is produced from metabolism of retinol to retinaldehyde by retinol dehydrogenase (RDH), followed by metabolism of retinaldehyde to RA by retinaldehyde dehydrogenase (RALDH). Previous studies on Raldh2-/- and Raldh3-/- mice demonstrated an RA requirement for gamma-aminobutyric acid (GABA)ergic and dopaminergic differentiation in forebrain basal ganglia, but no RA requirement was observed during early forebrain patterning or subsequent forebrain cortical expansion. However, other studies suggested that RA controls forebrain patterning, and analysis of ethylnitrosourea-induced Rdh10 mutants suggested that RA synthesized in the meninges stimulates forebrain cortical expansion. Results: We generated Rdh10-/- mouse embryos that lack RA activity early in the head and later in the meninges. We observed defects in hindbrain patterning and eye RA signaling, but early forebrain patterning was unaffected. Retinaldehyde treatment of Rdh10-/- embryos from E7-E9 rescues a cranial skeletal defect, resulting in E14.5 embryos lacking meningeal RA activity but maintaining normal forebrain shape and cortical expansion. Conclusions: Rdh10-/- embryos demonstrate that RA controls hindbrain but not early forebrain patterning, while studies on retinaldehyde-rescued Rdh10-/- embryos show that meningeal RA synthesis is unnecessary to stimulate forebrain cortical expansion. Developmental Dynamics 242:1056-1065, 2013. (C) 2013 Wiley Periodicals, Inc.