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Updated: Aug 6, 2026
Generation of Maternal Mutants Using zpc:cas9 Knock-in Zebrafish
Published on: July 22, 2025
Tob1 controls dorsal development of zebrafish embryos by antagonizing maternal beta-catenin transcriptional activity
Bo Xiong1, Yanning Rui, Min Zhang
1State 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.
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.
Insights
Zebrafish Tob1a protein is crucial for embryonic patterning. It inhibits beta-catenin signaling, a key pathway for dorsal development, by preventing crucial protein complex formation.
Area of Science:
- Developmental biology
- Molecular signaling pathways
- Embryogenesis
Background:
- Maternal beta-catenin and Nodal signals are vital for dorsal organizer formation and subsequent dorsal tissue development in vertebrate embryos.
- Tob (Transducer of ErbB2) proteins are known for antiproliferative effects and influence on BMP signaling, but their role in broader embryonic patterning remained unclear.
Purpose of the Study:
- To investigate the role of zebrafish tob1a in embryonic dorsoventral patterning.
- To elucidate the molecular mechanisms by which Tob1a influences key developmental signaling pathways.
Main Methods:
- Utilized zebrafish as a model organism to study embryonic patterning.
- Investigated protein-protein interactions between Tob1a and beta-catenin.
- Assessed the impact of Tob1a on beta-catenin and Nodal signaling transcriptional activity.
Main Results:
- Zebrafish tob1a is essential for proper dorsoventral patterning.
- Tob1a physically interacts with beta-catenin, inhibiting its transcriptional activity by blocking beta-catenin/LEF1 complex formation.
- Tob1a also inhibits Nodal effector Smad3 activity, but its primary role in limiting dorsal development is through antagonizing beta-catenin signaling.
Conclusions:
- Tob1a acts as a critical regulator of embryonic dorsoventral patterning by antagonizing beta-catenin signaling.
- The findings reveal a novel mechanism for controlling embryonic development through Tob protein interactions.
- Tob family members exhibit conserved biochemical properties and biological functions across species.
