Effect of retinoic acid signaling on Ripply3 expression and pharyngeal arch morphogenesis in mouse embryos
Effect of retinoic acid signaling on Ripply3 expression and pharyngeal arch morphogenesis in mouse embryos
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DOI：
10.1002/dvdy.301
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发表时间：
2021-01-25
影响因子：
2.5
通讯作者：
Takada, Shinji
中科院分区：
文献类型：
--
作者：
Okubo, Tadashi;Hara, Keiko;Takada, Shinji
咽部弓（PA）是按前后顺序依次产生的。Ripply3对小鼠胚胎后PA发育至关重要，在每个PA形成之前，其表达在外胚层和内胚层依次激活。由于Ripply3基因敲除（KO）小鼠的PA表型与维甲酸（RA）信号缺失的胚胎相似，我们研究了小鼠胚胎中RA信号与Ripply3的关系。结果在BMS493 （pan-RAR拮抗剂）处理的第三和第四PA发育缺陷的胚胎中，在E9.0时PA2后区域Ripply3表达降低。该表达式保持不变，其分布在E9.5处向后扩展。相反，高剂量RA暴露在E9.0和9.5时没有明显改变其表达。敲除视黄醛脱氢酶2 （Raldh2）导致更严重的PA缺陷，从而减弱Ripply3在PA1上的序列表达，降低其表达水平。由6kb Ripply3启动子片段驱动的EGFP报告基因表达重现了野生型PA发育过程中内源性Ripply3 mRNA的表达，但其分布在bms493处理和Raldh2 KO胚胎中扩展。结论RA信号对Ripply3表达的时空调控是小鼠后侧PA发育不可缺少的。
Background Pharyngeal arches (PA) are sequentially generated in an anterior-to-posterior order. Ripply3 is essential for posterior PA development in mouse embryos and its expression is sequentially activated in ectoderm and endoderm prior to formation of each PA. Since the PA phenotype of Ripply3 knockout (KO) mice is similar to that of retinoic acid (RA) signal-deficient embryos, we investigated the relationship between RA signaling and Ripply3 in mouse embryos.Results In BMS493 (pan-RAR antagonist) treated embryos, which are defective in third and fourth PA development, Ripply3 expression is decreased in the region posterior to PA2 at E9.0. This expression remains and its distribution is expanded posteriorly at E9.5. Conversely, high dose RA exposure does not apparently change its expression at E9.0 and 9.5. Knockout of retinaldehyde dehydrogenase 2 (Raldh2), which causes more severe PA defect, attenuates sequential Ripply3 expression at PA1 and reduces its expression level. EGFP reporter expression driven by a 6 kb Ripply3 promoter fragment recapitulates the endogenous Ripply3 mRNA expression during PA development in wild-type, but its distribution is expanded posteriorly in BMS493-treated and Raldh2 KO embryos.Conclusion Spatio-temporal regulation of Ripply3 expression by RA signaling is indispensable for the posterior PA development in mouse.