title: Tob1 controls dorsal development of zebrafish embryos by antagonizing maternal beta-catenin transcriptional activity.
abstract: Maternal beta-catenin and Nodal signals are essential for the formation of the dorsal organizer, which, in turn, induces neural and other dorsal tissue development in vertebrate embryos. Tob (Transducer of ErbB2) proteins possess antiproliferative properties and are known to influence BMP signaling, but their relationship to other signaling pathways and to embryonic patterning in general was unclear. In this study, we demonstrate that zebrafish tob1a is required for correct dorsoventral patterning. Mechanistically, Tob1a inhibits beta-catenin transcriptional activity by physically associating with beta-catenin and preventing the formation of beta-catenin/LEF1 complexes. Although Tob1a can also inhibit the transcriptional activity of the Nodal effector Smad3, its role in limiting dorsal development is executed primarily by antagonizing the beta-catenin signal. We further demonstrate that Tob family members across species share similar biochemical properties and biological activities.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Protein Sciences Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiong
authors.forename: Yanning
authors.initials: Y
authors.lastname: Rui
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Kehui
authors.initials: K
authors.lastname: Shi
authors.forename: Shunji
authors.initials: S
authors.lastname: Jia
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.forename: Kun
authors.initials: K
authors.lastname: Yin
authors.forename: Huizhe
authors.initials: H
authors.lastname: Huang
authors.forename: Shuyong
authors.initials: S
authors.lastname: Lin
authors.forename: Xingang
authors.initials: X
authors.lastname: Zhao
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Chen
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
authors.forename: Sheng-Cai
authors.initials: SC
authors.lastname: Lin
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000494:pharmacology / Q000502:physiology*; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
chemical_list: D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D051176:beta Catenin; C496416:tob1a protein, zebrafish