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- Title
Effect of retinoic acid signaling on Ripply3 expression and pharyngeal arch morphogenesis in mouse embryos.
- Authors
Okubo, Tadashi; Hara, Keiko; Azuma, Sadahiro; Takada, Shinji
- Abstract
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. Key Findings: Treatment with BMS493 (pan‐RAR antagonist) caused the severe deficiency of third and forth pharyngeal arches and the temporal decrease of Ripply3 expression in the posterior region of PA2 at E9.0.Retinaldehyde dehydrogenase 2 (Raldh2) KO mouse embryos displayed attenuation of PA development and reduction of Ripply3 expression.EGFP reporter transgene, driven by the defined promoter fragment of Ripply3, recapitulates the endogenous expression of Ripply3 mRNA in mouse embryos, and EGFP reporter activity was affected in BMS493 treated or Raldh2 KO mouse embryos.Spatio‐temporal regulation of Ripply3 expression by RA signaling is indispensable for the posterior pharyngeal arch development in mouse.
- Subjects
TRETINOIN; EMBRYOS; MORPHOGENESIS; MICE; ECTODERM
- Publication
Developmental Dynamics, 2021, Vol 250, Issue 7, p1036
- ISSN
1058-8388
- Publication type
Article
- DOI
10.1002/dvdy.301