Tnfrsf10 Signaling is Required to Maintain the Stem Cell Niche in the Zebrafish Lateral Line

Area of Science:

• Developmental biology
• Cell biology
• Regenerative medicine

Background:

• Mammalian inner ear hair cells have limited regeneration.
• Zebrafish lateral line neuromasts exhibit robust hair cell regeneration.
• Stem cell populations and self-renewal mechanisms in neuromasts are not fully understood.

Purpose of the Study:

• Identify stem cell populations in zebrafish neuromasts.
• Elucidate the mechanism of hair cell regeneration and stem cell self-renewal.
• Investigate the role of TNF superfamily signaling in neuromast regeneration.

Main Methods:

• Zebrafish genetic mutation analysis (tnfrsfa).
• Analysis of neuromast sensory organ and hair cell regeneration.
• Investigation of cell populations peripheral to neuromasts, including mantle cells.
• Study of TNF ligands (Tnfsf10, Tnfsf10l3) and their receptor (Tnfrsfa).
• Analysis of NF-κB signaling pathway activation and SOX2 expression.

Main Results:

• Mutation in tnfrsfa caused neuromast depletion and impaired hair cell regeneration.
• Peripheral cells, termed mantle cells, were identified as potential stem cells.
• TNF superfamily ligands (TRAIL) signal through Tnfrsfa to activate NF-κB in mantle cells non-cell-autonomously.
• NF-κB signaling is essential for maintaining mantle cell identity via SOX2 expression.

Conclusions:

• Mantle cells function as stem cells in zebrafish neuromasts.
• TNF superfamily signaling, specifically TRAIL/Tnfrsfa/NF-κB, is critical for stem cell maintenance.
• This pathway is crucial for the remarkable hair cell regeneration capacity in zebrafish.