title: Proper closure of the optic fissure requires ephrin A5-EphB2-JNK signaling.
abstract: The development of complex organs such as the eye requires a delicate and coordinated balance of cell division and cell death. Although apoptosis is prevalent in the proximoventral optic cup, the precise role it plays in eye development needs to be investigated further. In this study, we show that reduced apoptosis in the proximoventral optic cup prevents closure of the optic fissure. We also show that expression of ephrin A5 (Efna5) partially overlaps with Eph receptor B2 (Ephb2) expression in the proximoventral optic cup and that binding of EphB2 to ephrin A5 induces a sustained activation of JNK. This prolonged JNK signal promotes apoptosis and prevents cell proliferation. Thus, we propose that the unique cross-subclass interaction of EphB2 with ephrin A5 has evolved to function upstream of JNK signaling for the purpose of maintaining an adequate pool of progenitor cells to ensure proper closure of the optic fissure.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Chungpa-ro 47gil 100, Yongsan-gu, Seoul 140-742, Korea.
authors.forename: Hyuna
authors.initials: H
authors.lastname: Noh
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Chungpa-ro 47gil 100, Yongsan-gu, Seoul 140-742, Korea.
authors.forename: Haeryung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Chungpa-ro 47gil 100, Yongsan-gu, Seoul 140-742, Korea.
authors.forename: Eunjeong
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Chungpa-ro 47gil 100, Yongsan-gu, Seoul 140-742, Korea scpark@sookmyung.ac.kr.
authors.forename: Soochul
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000378:metabolism; D004789:Enzyme Activation; D036386:Ephrin-A5 / Q000172:deficiency / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008822:Mice, Transgenic; D008954:Models, Biological; D009024:Morphogenesis; D009898:Optic Disk / Q000196:embryology* / Q000378:metabolism*; D036183:Receptor, EphB2 / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D036386:Ephrin-A5; D036183:Receptor, EphB2
keywords: Apoptosis; MAPK; Optic cup; Optic fissure closure