A conserved pituitary response to tissue loss controls regeneration across vertebrates
Regenerating complex tissues requires coordination between local cellular responses and body-wide systemic signals. As a central endocrine regulator, the pituitary is well positioned to coordinate this process. Here, we identify the pituitary as an injury-responsive regulator of axolotl limb and tilapia fin regeneration. Limb loss triggered sustained transcriptional responses in the axolotl pituitary. Single-cell transcriptomics linked pituitary loss to altered gene expression in prolactin- and growth hormone-responsive limb cells. Local disruption of the prolactin receptor impaired digit formation, whereas combined hormone treatment partially restored regeneration in hypophysectomized axolotls. In tilapia, pituitary removal impaired fin regeneration and prolactin-related signaling. Mouse digits differed from axolotls and tilapia in how and when they received pituitary signals during regeneration, suggesting pituitary-dependent regrowth is evolutionarily divergent among highly regenerative vertebrates.
Authors
- Ryan T. Kim (ORCID: https://orcid.org/0009-0007-3920-4982)
- Ryan J. A. Chang (ORCID: https://orcid.org/0000-0003-1324-0751)
- Julia C. Paoli (ORCID: https://orcid.org/0000-0001-8266-1766)
- Tyler R. Goodearly (ORCID: https://orcid.org/0009-0001-1137-242X)
- Jessica A. Lehoczky (ORCID: https://orcid.org/0000-0002-9210-2922)
- Jason P. Breves (ORCID: https://orcid.org/0000-0003-1193-4389)
- André P. Seale (ORCID: https://orcid.org/0000-0003-2398-4201)
- Michael J. Raymond
- Anne S. Golding
- Erica Chen (ORCID: https://orcid.org/0009-0000-7273-2081)
- Jessica L. Whited (ORCID: https://orcid.org/0000-0002-3709-6515)
- Duygu Payzin‐Dogru (ORCID: https://orcid.org/0000-0002-3717-0244)
- Bradley K. Fox (ORCID: https://orcid.org/0009-0003-0502-4634)
- Noah Lopez (ORCID: https://orcid.org/0000-0001-7005-298X)
- Reilly S. Merlo (ORCID: https://orcid.org/0009-0003-4839-0634)
- S. Y. Celeste Wu (ORCID: https://orcid.org/0009-0008-3275-6052)
- Anna G. Luong (ORCID: https://orcid.org/0009-0003-0205-2146)
- Hani D. Singer (ORCID: https://orcid.org/0009-0001-7722-2758)
- Tim Froitzheim (ORCID: https://orcid.org/0009-0002-8878-0883)
- Anthony E. Striker (ORCID: https://orcid.org/0009-0001-2608-4009)
- Matthew Chen
- Laurel Shugart (ORCID: https://orcid.org/0009-0004-3817-9197)
- Tia S. Patel (ORCID: https://orcid.org/0009-0005-9737-4213)
- Ashley R. Juarez (ORCID: https://orcid.org/0009-0002-8539-9470)
- Anne T. Harrington
- Emily de Rezende
- Miranda X. Thai
- Antzela Zgouro
- Luciana Landivar-Uriona
- Ava R. Moss
Institutions
- Brigham and Women's Hospital (US)
- Northeastern University (US)
- Karolinska University Hospital (SE)
- Harvard University (US)
- Skidmore College (US)
- Heidelberg University (DE)
- Karolinska Institutet (SE)
- Universidad Católica Bolivia San Pablo (BO)
- Universidad Católica San Pablo (PE)
- Heidelberg University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-02
- DOI
- https://doi.org/10.64898/2026.10.31.762810
- Primary Topic
- Planarian Biology and Electrostimulation
- Type
- preprint