Hcfc1 and Ogt Mediate Zebrafish <scp>CNS</scp> Regeneration Through Hippo/Yap Signalling
Regeneration of the central nervous system (CNS) is a complex and tightly regulated process, yet the precise molecular players and transcriptional regulators involved remain incompletely understood. Here, we identify Host Cell Factor-1 (Hcfc1), a transcriptional co-regulator, and O-GlcNAc transferase (Ogt), which cleaves and O-GlcNAcylates HCF-1, as crucial regulators of zebrafish brain and retinal regeneration. We uncover their interplay with the Hippo/Yap signalling pathway, a well-known regulator of tissue growth and repair. Knockdown of hcfc1a/b or Ogt activity inhibition disrupts regeneration and reduces Yap levels, while Yap inhibition alone also impairs regeneration. Strikingly, overexpression of constitutively active Yap5SA rescues proliferation defects caused by Hcfc1 depletion and Ogt inhibition in retinal regeneration. Further, yap1 knockdown reduces hcfc1a/b levels, suggesting potential feedback regulation. These findings reveal a previously unrecognised regulatory axis involving Hcfc1, Ogt, and the Hippo/Yap pathway, which governs CNS regeneration. Targeting this pathway could offer a strategy for enhancing CNS regeneration.
Authors
- Poonam Sharma (ORCID: https://orcid.org/0000-0002-3725-3509)
- Rajesh Ramachandran (ORCID: https://orcid.org/0000-0002-4645-2841)
- S. Bhasin (ORCID: https://orcid.org/0000-0002-4536-1649)
- Suhel Parvez (ORCID: https://orcid.org/0000-0002-6318-6506)
- Priyanka P. Srivastava (ORCID: https://orcid.org/0009-0005-8437-0694)
- Ayushma
- Shilpi Minocha (ORCID: https://orcid.org/0000-0001-8229-1443)
- Omkar Mahadeo Desai (ORCID: https://orcid.org/0009-0000-1526-1877)
- Rohan Chakraborty (ORCID: https://orcid.org/0000-0003-4544-8311)
- Kshitiz Yadav (ORCID: https://orcid.org/0009-0000-9620-2018)
Institutions
- Indian Institute of Science Education and Research Mohali (IN)
- Jamia Hamdard (IN)
- Helmholtz Centre for Infection Research (DE)
- Indian Institute of Technology Delhi (IN)
- Technische Universität Dresden (DE)
Publication Details
- Journal
- Cell Proliferation
- Published
- 2025-10-17
- DOI
- https://doi.org/10.1111/cpr.70132
- Citations
- 1
- Primary Topic
- Hippo pathway signaling and YAP/TAZ
- Type
- article
- Field-Weighted Citation Impact
- 1.15
Funders
- Indian Institute of Science
- National Research Foundation
- Department of Biotechnology, Ministry of Science and Technology, India
- Department of Science and Technology, Ministry of Science and Technology, India
- Indo-French Centre for the Promotion of Advanced Research
- Indian Institute of Technology Delhi
- Indian Institute of Science Education and Research Mohali