title: EphA/ephrin-A signaling is critically involved in region-specific apoptosis during early brain development.
abstract: EphAs and ephrin-As have been implicated in the morphogenesis of the developing brain. We found that EphA7 and ephrin-A5 are coexpressed in the dorsal midline (DM) of the diencephalon and anterior mesencephalon. Interestingly, programmed cell death (PCD) of the neural epithelial cells normally found in this region was reduced in ephrin-A5/ephrin-A2 dual-deficient embryos. In contrast, in vivo expression of ephrin-A5-Fc or full-length ephrin-A5 strongly induced apoptosis in neural epithelial cells and was accompanied by severe brain malformation during embryonic development. Expression of ephrinA5-Fc correlated with apoptosis of EphA7-expressing cells, whereas null mutation of ephrin-A5 resulted in the converse phenotype. Importantly, null mutation of caspase-3 or endogenous ephrin-A5 attenuated the PCD induced by ectopically overexpressed ephrin-A5. Together, our results suggest that brain region-specific PCD may occur in a region where EphAs cluster with neighboring ephrin-As through cell-cell contact.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-gu, Seoul 140-742, Korea.
authors.forename: E
authors.initials: E
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Noh
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Yoo
authors.forename: S
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D004027:Diencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D036383:Ephrin-A2 / Q000378:metabolism*; D036386:Ephrin-A5 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D036141:Receptor, EphA7 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D036383:Ephrin-A2; D036386:Ephrin-A5; D036141:Receptor, EphA7