Retinoic Acid Signaling In Zebrafish: Heart And Craniofacial Cartilage Development

This study investigates how retinoic acid signaling regulates the development of cardiac progenitor cells and craniofacial neural crest cells in zebrafish, aiming to clarify the early developmental relationship between craniofacial pharyngeal arch cartilage and the heart, and providing insights into congenital heart disease and craniofacial skeletal disorders. Tg (sox10: GFP) and Tg (col2a1a: Dendra2-NTR) zebrafish (Danio rerio) embryos were used as model systems. In vivo imaging, Alcian blue staining, H&E staining, oxidative stress detection, proliferating cell nuclear antigen (PCNA) antibody staining, quantitative PCR, ROS assay kit assays, MDA assay and RNA sequencing were employed to comprehensively analyze the relationship between craniofacial pharyngeal arch cartilage and the heart development. (approval: gnnu2022–0628) RA signaling inhibition decreased ALDH activity, elevated ROS levels, and induced oxidative stress, leading to DNA damage in zebrafish. This disruption impaired neural crest cell migration, proliferation, and differentiation, causing craniofacial cartilage malformations. RA signaling also regulates endoderm development, cardiac progenitor migration, and neural crest contributions to heart formation. Our study demonstrates that RA signaling is essential for the proper migration of myocardial progenitor cells and neural crest cells during early zebrafish development. Disruption of this pathway leads to cardiac bifida and craniofacial cartilage malformations, highlighting the crucial role of RA signaling in heart and cartilage formation. These findings provide new insights into the molecular mechanisms underlying congenital heart and craniofacial defects, offering potential targets for future therapeutic interventions.