title: Tbx2 regulates anterior neural specification by repressing FGF signaling pathway.
abstract: During early embryogenesis, FGF signals regulate the antero-posterior (AP) patterning of the neural plate by promoting posterior cell fates. In particular, BMP signal-mediated attenuation of FGF pathway plays a critical role in the determination of the anterior neural region. Here we show that Tbx2, a T-box transcriptional repressor regulates anterior neural specification by suppressing FGF8 signaling pathway in Xenopus embryo. Tbx2 is expressed in the anterior edge of the neural plate in early neurulae. Overexpression and knockdown of Tbx2 induce expansion and reduction in the expression of anterior neural markers, respectively. It also suppresses FGF8-induced ERK phosphorylation and neural caudalization. Tbx2, which is a target gene of BMP signal, down-regulates FGF8 signaling by inhibiting the expression of Flrt3, a positive regulator of this pathway. We found that Tbx2 binds directly to the T-box element located in the promoter region of Flrt3 gene, thereby interfering with the activity of the promoter. Consistently, Tbx2 augmentation of anterior neural formation is inhibited by co-expression of Flrt3. Furthermore, disruption of the anterior-most structures such as eyes in Tbx2-depleted embryos can be rescued by inhibition of Flrt3 function or FGF signaling. Taken together, our results suggest that Tbx2 mediates BMP signal to down-regulate FGF signaling pathway by repressing Flrt3 expression for anterior tissue formation.
authors.affiliation: Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Republic of Korea.
authors.forename: Gun-Sik
authors.initials: GS
authors.lastname: Cho
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Pungnap-Dong, Songpa-Gu, Seoul 138-736, Republic of Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Pungnap-Dong, Songpa-Gu, Seoul 138-736, Republic of Korea. Electronic address: choisc@amc.seoul.kr.
authors.forename: Sun-Cheol
authors.initials: SC
authors.lastname: Choi
authors.affiliation: Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Republic of Korea. Electronic address: jkh@postech.ac.kr.
authors.forename: Jin-Kwan
authors.initials: JK
authors.lastname: Han
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000196:embryology; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; C542073:FLRT3 protein, Xenopus; D008565:Membrane Proteins; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors
keywords: FGF; Flrt3; Forebrain; Neural patterning; Tbx2; Xenopus