title: Pea3 determines the isthmus region at the downstream of Fgf8-Ras-ERK signaling pathway.
abstract: It has been shown that strong Fgf8 signal activates Ras-ERK signaling pathway to determine metencephalon, which consists of rhombomere 1 (r1), where the cerebellum differentiates, and isthmus (r0). The present study was undertaken to check if Ets type transcription factor Pea3 functions downstream of Ras-ERK signaling to determine metencephalon. Pea3 misexpression resulted in repression of Otx2 expression in the mesencephalon, induction of Gbx2 and Fgf8 expression in the mesencephalon, and differentiation of the trochlear neurons in the posterior mesencephalon. Fate change of the tectum to the cerebellum did not occur. Repression of Pea3 function by misexpressing the chimeric molecule of Engrailed repressor domain EH1 and Pea3 (eh1-Pea3) resulted in induction of Otx2 expression in the metencephalon, repression of Gbx2 and Fgf8 expression in the metencephalon, and differentiation of the oculomotor neurons in the isthmus. It was concluded that Pea3 plays a pivotal role in determination of the isthmus (r0) property downstream of Fgf8-Ras-ERK signaling.
authors.affiliation: Department of Molecular Neurobiology, Institute of Development, Aging & Cancer and Graduate School of Life Sciences, Tohoku University, Sendai, 980-8575, Miyagi, Japan.
authors.forename: Hidekiyo
authors.initials: H
authors.lastname: Harada
authors.affiliation: Department of Molecular Neurobiology, Institute of Development, Aging & Cancer and Graduate School of Life Sciences, Tohoku University, Sendai, 980-8575, Miyagi, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Omi
authors.affiliation: Department of Molecular Neurobiology, Institute of Development, Aging & Cancer and Graduate School of Life Sciences, Tohoku University, Sendai, 980-8575, Miyagi, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Molecular Neurobiology, Institute of Development, Aging & Cancer and Graduate School of Life Sciences, Tohoku University, Sendai, 980-8575, Miyagi, Japan.
authors.forename: Harukazu
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D002645:Chickens; D015536:Down-Regulation; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; C065788:transcription factor PEA3; D005346:Fibroblast Growth Factors; D018631:ras Proteins
keywords: Ets-Pea3 subfamily; FGF-Ras-ERK pathway; Isthmus; Pea3