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使用视黄醛挽救的 Rdh10 敲除小鼠研究视黄酸在胚胎大脑发育过程中的功能。

Investigation of retinoic acid function during embryonic brain development using retinaldehyde-rescued Rdh10 knockout mice.

机构信息

Sanford-Burnham Medical Research Institute, La Jolla, California, USA.

出版信息

Dev Dyn. 2013 Sep;242(9):1056-65. doi: 10.1002/dvdy.23999. Epub 2013 Jul 22.

DOI:10.1002/dvdy.23999
PMID:23765990
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3877746/
Abstract

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 γ-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.

摘要

背景

维甲酸（RA）信号在小脑后区控制着模式形成和神经元分化，但前脑 RA 功能仍存在争议。RA 是由视黄醇脱氢酶（RDH）将视黄醇代谢为视醛，然后由视醛脱氢酶（RALDH）将视醛代谢为 RA 产生的。先前关于 Raldh2-/-和 Raldh3-/-小鼠的研究表明，RA 在大脑基底神经节的γ-氨基丁酸（GABA）能和多巴胺能分化中是必需的，但在早期前脑模式形成或随后的前脑皮质扩张过程中没有观察到 RA 的需求。然而，其他研究表明 RA 控制着前脑的模式形成，对乙基亚硝脲诱导的 Rdh10 突变体的分析表明，脑膜中合成的 RA 刺激了前脑皮质的扩张。

结果

我们生成了 Rdh10-/-鼠胚胎，这些胚胎在头部早期和脑膜后期缺乏 RA 活性。我们观察到小脑后区模式形成和眼睛 RA 信号的缺陷，但早期前脑模式形成不受影响。Rdh10-/-胚胎从 E7-E9 进行视醛处理可挽救颅面骨骼缺陷，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 控制着小脑，但不控制早期前脑的模式形成，而对视网膜醛挽救的 Rdh10-/-胚胎的研究表明，脑膜 RA 合成对于刺激前脑皮质扩张是不必要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/1db2a9e462fa/nihms538584f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/c5875af794b7/nihms538584f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/8e20a6dcb4b8/nihms538584f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/484e4b12dc08/nihms538584f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/50d557df5282/nihms538584f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/1db2a9e462fa/nihms538584f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/c5875af794b7/nihms538584f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/8e20a6dcb4b8/nihms538584f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/484e4b12dc08/nihms538584f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/50d557df5282/nihms538584f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ae/3877746/1db2a9e462fa/nihms538584f5.jpg

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