PUBLICATION
Cytoneme-mediated intercellular signaling in keratinocytes is essential for epidermal remodeling in zebrafish
- Authors
- Wang, Y., Nguyen, T., He, Q., Has, O., Forouzesh, K., Eom, D.S.
- ID
- ZDB-PUB-250807-2
- Date
- 2025
- Source
- eLIFE 13: (Journal)
- Registered Authors
- Eom, Dae Seok
- Keywords
- IL-17, airinemes, cytonemes, developmental biology, epidermis, keratinocytes, notch, zebrafish
- MeSH Terms
-
- Humans
- Signal Transduction*
- Animals
- Keratinocytes*/cytology
- Keratinocytes*/metabolism
- Keratinocytes*/physiology
- Zebrafish*
- Receptors, Notch/metabolism
- Cell Differentiation
- Zebrafish Proteins/metabolism
- Cell Proliferation
- Epidermis*/metabolism
- Epidermis*/physiology
- Epidermal Cells
- Pseudopodia*/metabolism
- PubMed
- 40767593 Full text @ Elife
Citation
Wang, Y., Nguyen, T., He, Q., Has, O., Forouzesh, K., Eom, D.S. (2025) Cytoneme-mediated intercellular signaling in keratinocytes is essential for epidermal remodeling in zebrafish. eLIFE. 13:.
Abstract
The skin, the largest organ, functions as a primary defense mechanism. Epidermal stem cells supply undifferentiated keratinocytes that differentiate as they migrate toward the outermost skin layer. Although such a replenishment process is disrupted in various human skin diseases, its underlying mechanisms remain elusive. With high-resolution live imaging and in vivo manipulations, we revealed that Notch signaling between keratinocytes is mediated by signaling filopodia called cytonemes and is essential for proper keratinocyte differentiation and proliferation. Inhibiting keratinocyte cytonemes reduced Notch expression within undifferentiated keratinocytes, leading to abnormal differentiation and hyperproliferation, resembling human skin disease phenotypes. Overproduction of Interleukin (IL)-17 signal, associated with skin diseases like psoriasis, induces psoriatic phenotypes by reducing cytoneme extension in zebrafish. Our study suggests that intercellular signaling between keratinocytes through cytonemes is critical for epidermal maintenance, and its misregulation could be an origin of human skin diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping