Flavins in Focus: Vitamin B2 as a Metabolic Keystone for Neuronal Repair in Regenerating Planarians
- 1Centre for Environmental Sciences; Zoology: Biodiversity and Toxicology, Hasselt University; Diepenbeek, Belgium.
Abstract
Regeneration imposes substantial metabolic demands to support the reconstruction of functional tissues. Essential vitamins are indispensable metabolic cofactors, yet whether their availability is spatially organized to support local metabolic demands within regenerative tissues remains largely unknown. Here, we identify previously undescribed flavin-rich cells, referred to as 'flavinocytes', that form an extensive network that spatially organizes vitamin B2 metabolism in the planarian Schmidtea mediterranea. Using endogenous flavin autofluorescence as a label-free in vivo metabolic readout, we show that this network consists of elongated cells that form longitudinal varicosity-containing strands closely associated with the central nervous system. RNAi-mediated disruption of riboflavin uptake and metabolism reduced flavin-associated autofluorescence and its spatial distribution within the animal, while affecting blastema formation, eye regeneration, and nervous system reconstruction. These findings demonstrate that riboflavin metabolism is required for successful regeneration. Single-cell transcriptomics, protein localization, and functional perturbations further suggest a reciprocal relationship between flavinocytes and the regenerating nervous system, pointing to coordinated neuro-metabolic interactions during tissue repair. Together, our findings demonstrate the importance of riboflavin metabolism for nervous system regeneration and provide new insight into the spatial organization of metabolism during tissue regeneration.
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BibTeX
@misc{heleven2026flavins,
title = {{Flavins in Focus: Vitamin B2 as a Metabolic Keystone for Neuronal Repair in Regenerating Planarians}},
author = {M. Heleven and V. Jaenen and R. Maes and J. F. Abril and R. Voglar and C. Segnana and T. Artois and N. D. Saenen and F. Cebria and K. Smeets},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.12.758197},
url = {https://www.biorxiv.org/content/10.64898/2026.10.12.758197v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Flavins in Focus: Vitamin B2 as a Metabolic Keystone for Neuronal Repair in Regenerating Planarians
AU - M. Heleven
AU - V. Jaenen
AU - R. Maes
AU - J. F. Abril
AU - R. Voglar
AU - C. Segnana
AU - T. Artois
AU - N. D. Saenen
AU - F. Cebria
AU - K. Smeets
PY - 2026
DA - 2026/10/12
PB - bioRxiv
DO - 10.64898/2026.10.12.758197
UR - https://www.biorxiv.org/content/10.64898/2026.10.12.758197v1
AB - Regeneration imposes substantial metabolic demands to support the reconstruction of functional tissues. Essential vitamins are indispensable metabolic cofactors, yet whether their availability is spatially organized to support local metabolic demands within regenerative tissues remains largely unknown. Here, we identify previously undescribed flavin-rich cells, referred to as 'flavinocytes', that form an extensive network that spatially organizes vitamin B2 metabolism in the planarian Schmidtea mediterranea. Using endogenous flavin autofluorescence as a label-free in vivo metabolic readout, we show that this network consists of elongated cells that form longitudinal varicosity-containing strands closely associated with the central nervous system. RNAi-mediated disruption of riboflavin uptake and metabolism reduced flavin-associated autofluorescence and its spatial distribution within the animal, while affecting blastema formation, eye regeneration, and nervous system reconstruction. These findings demonstrate that riboflavin metabolism is required for successful regeneration. Single-cell transcriptomics, protein localization, and functional perturbations further suggest a reciprocal relationship between flavinocytes and the regenerating nervous system, pointing to coordinated neuro-metabolic interactions during tissue repair. Together, our findings demonstrate the importance of riboflavin metabolism for nervous system regeneration and provide new insight into the spatial organization of metabolism during tissue regeneration.
ER -