title: In vivo expression of ephrinA5-Fc in mice results in cephalic neural crest agenesis and craniofacial abnormalities.
abstract: Eph receptors and their ligands ephrins have been implicated in guiding the directed migration of neural crest cells (NCCs). In this study, we found that Wnt1-Cre-mediated expression of ephrinA5-Fc along the dorsal midline of the dien- and mesencephalon resulted in severe craniofacial malformation of mouse embryo. Interestingly, expression of cephalic NCC markers decreased significantly in the frontonasal process and branchial arches 1 and 2, which are target areas for the migratory cephalic NCCs originating in the dien- and mesencephalon. In addition, these craniofacial tissues were much smaller in mutant embryos expressing ephrinA5-Fc. Importantly, EphA7-positive cephalic NCCs were absent along the dorsal dien- and mesencephalon of mutant embryos expressing ephrinA5-Fc, suggesting that the generation of cephalic NCCs is disrupted due to ephrinA5-Fc expression. NCC explant experiments suggested that ephrinA5-Fc perturbed survival of cephalic NCC precursors in the dorsal midline tissue rather than affecting their migratory capacity, which was consistent with our previous report that expression of ephrinA5-Fc in the dorsal midline is responsible for severe neuroepithelial cell apoptotic death. Taken together, our findings strongly suggest that expression of ephrinA5-Fc decreases a population of cephalic NCC precursors in the dorsal midline of the dien- and mesencephalon, thereby disrupting craniofacial development in the mouse embryos.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Hyuna
authors.initials: H
authors.lastname: Noh
authors.forename: Eunjeong
authors.initials: E
authors.lastname: Park
authors.forename: Soochul
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D002465:Cell Movement; D019465:Craniofacial Abnormalities / Q000378:metabolism*; D004622:Embryo, Mammalian; D036386:Ephrin-A5 / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D008822:Mice, Transgenic; D009432:Neural Crest / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D036141:Receptor, EphA7 / Q000378:metabolism
chemical_list: D036386:Ephrin-A5; D036141:Receptor, EphA7