Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration
- Sun Yat-Sen Memorial Hospital, China
- Sun Yat-Sen University, China
Abstract
The sox2 expressing (sox2+) progenitors in adult mammalian inner ear lose the capacity to regenerate while progenitors in the zebrafish lateral line are able to proliferate and regenerate damaged HCs throughout lifetime. To mimic the HC damage in mammals we have established a zebrafish severe injury model to eliminate both progenitors and HCs. The atoh1a expressing (atoh1a+) HC precursors were the main population that survived post severe injury, and gained sox2 expression to initiate progenitor regeneration. In response to severe injury, yap was activated to upregulate lin28a transcription. Severe-injury-induced progenitor regeneration was disabled in lin28a or yap mutants. In contrary, overexpression of lin28a initiated the recovery of sox2+ progenitors. Mechanistically, microRNA let7 acted downstream of lin28a to activate Wnt pathway for promoting regeneration. Our findings that lin28a is necessary and sufficient to regenerate the exhausted sox2+ progenitors shed light on restoration of progenitors to initiate HC regeneration in mammals.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Ministry of Science and Technology of the People's Republic of China (National Key R&D Program of China,2018YFA0108304)
- Linjia Jiang
National Science Foundation (Youth Project,81800164)
- Linjia Jiang
National Science Foundation (General Project,31871467)
- Linjia Jiang
Guangdong Science and Technology Department (basic research project FF0C;2018A030313497)
- Linjia Jiang
Guangdong Science and Technology Department (The key Research and Development Program of Guangdong Province,2019B020234002)
- Meng Zhao
Shenzhen Foundation of Science and Technology (JCYJ20170818103626421)
- Meng Zhao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Ye et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration
eLife 9:e55771.
https://doi.org/10.7554/eLife.55771
