Affiliation:
1. The Key Laboratory of Virology of Guangzhou, Jinan University
2. First Affiliated Hospital, Jinan University
3. Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, China
Abstract
Proper retinoic acid (RA) signaling is essential for normal craniofacial development. Both excessive RA and RA deficiency in early embryonic stage may lead to a variety of craniofacial malformations, for example, cleft palate, which have been investigated extensively. Dysregulated Wnt and Shh signaling were shown to underlie the pathogenesis of RA-induced craniofacial defects. In our present study, we showed a spatiotemporal-specific effect of RA signaling in regulating early development of facial prominences. Although inhibited Wnt activities was observed in E12.5/E13.5 mouse palatal shelves, early exposure of excessive RA induced Wnt signaling and Wnt-related gene expression in E11.5/E12.5 mouse embryonic frontonasal/maxillary processes. A conserved regulatory network ofmiR-484-Fzd5was identified to play critical roles in RA-regulated craniofacial development using RNA-seq. In addition, subsequent osteogenic/chondrogenic differentiation were differentially regulated in discrete mouse embryonic facial prominences in response to early RA induction, demonstrated using both in vitro and in vivo analyses.
Funder
Natural Science Foundation of Guangdong Province
Publisher
Life Science Alliance, LLC
Subject
Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology