Tob1 controls dorsal development of zebrafish embryos by antagonizing maternal beta-catenin transcriptional activity.
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.
Xiong
Bo
B
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.
Rui
Yanning
Y
Zhang
Min
M
Shi
Kehui
K
Jia
Shunji
S
Tian
Tian
T
Yin
Kun
K
Huang
Huizhe
H
Lin
Shuyong
S
Zhao
Xingang
X
Chen
Yinghua
Y
Chen
Ye-Guang
YG
Lin
Sheng-Cai
SC
Meng
Anming
A
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
D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D051176:beta Catenin; C496416:tob1a protein, zebrafish