PUBLICATION

Pharmacological reprogramming of zebrafish lateral line supporting cells to a migratory progenitor state

Authors
Brooks, P.M., Lewis, P., Million-Perez, S., Yandulskaya, A.S., Khalil, M., Janes, M., Porco, J., Walker, E., Meyers, J.R.
ID
ZDB-PUB-240511-11
Date
2024
Source
Developmental Biology   512: 70-88 (Journal)
Registered Authors
Meyers, Jason
Keywords
Lateral Line, Neuromast, Zebrafish, epithelial-to-mesenchymal transition, mantle cell, regeneration, sensory hair cell, supporting cell
MeSH Terms
  • Animals
  • Cell Differentiation
  • Cell Movement*
  • Cellular Reprogramming
  • Fibroblast Growth Factors/metabolism
  • Lateral Line System*/cytology
  • Lateral Line System*/embryology
  • Signal Transduction
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • Wnt Signaling Pathway
  • Zebrafish*/embryology
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
38729405 Full text @ Dev. Biol.
Abstract
In the zebrafish lateral line, non-sensory supporting cells readily re-enter the cell cycle to generate new hair cells and supporting cells during homeostatic maintenance and following damage to hair cells. This contrasts with supporting cells from mammalian vestibular and auditory sensory epithelia which rarely re-enter the cell cycle, and hence loss of hair cells results in permanent sensory deficit. Lateral line supporting cells are derived from multipotent progenitor cells that migrate down the trunk midline as a primordium and are deposited to differentiate into a neuromast. We have found that we can revert zebrafish support cells back to a migratory progenitor state by pharmacologically altering the signaling environment to mimic that of the migratory primordium, with active Wnt signaling and repressed FGF signaling. The reverted supporting cells migrate anteriorly and posteriorly along the horizontal myoseptum and will re-epithelialize to form an increased number of neuromasts along the midline when the pharmacological agents are removed. These data demonstrate that supporting cells can be readily reprogrammed to a migratory multipotent progenitor state that can form new sensory neuromasts, which has important implications for our understanding of how the lateral line system matures and expands in fish and also suggest avenues for returning mammalian supporting cells back to a proliferative state.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping