Transcriptional coupling of metabolism and cell mechanics controls human neuroepithelium morphogenesis
Abstract
Tissue morphogenesis integrates developmental programs with cell mechanics, yet the mechanisms coupling these processes remain poorly understood. We investigated this link during neuroepithelial morphogenesis in human iPSC-derived dorsal spinal organoids. We found that PAX3, a transcription factor whose loss causes neural tube defects, promotes force-bearing adherens junction assembly. It does so by driving apical clustering of N-cadherin complexes, thereby enabling neuroepithelial morphogenesis, a function conserved in the mouse neural tube. Transcriptomic, metabolomic, and functional analyses show that PAX3 sustains upper glycolysis and the associated mannose-dependent glycosylation pathways. Exogenous mannose rescues cadherin clustering and adherens junction mechanics following PAX3 loss, whereas inhibition of glycolysis or glycosylation recapitulates these defects. These findings establish mannose metabolism as a PAX3-regulated pathway conferring mechanical competence to developing tissues.
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BibTeX
@misc{mirdass2026transcriptional,
title = {{Transcriptional coupling of metabolism and cell mechanics controls human neuroepithelium morphogenesis}},
author = {Camil Mirdass and Lucas Denis and Hugo Lachuer and Mikaëlle Bocel and Anis Bourou and Kamal Bouhali and Nicolas Valentin and Sandrine Adiba and Alice Marteil and Céline Chollet and Emeline Chu-Van and Xavier Baudin and Catherine Pioche-Durieu and Sarah Chebouti and Bruno Estebe and Frédéric Relaix and Florence Castelli and Valérie Dupe and Sébastien Léon and Stéphane Nedelec and Nicolas Borghi and Vanessa Ribes},
howpublished = {HAL},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.753382},
url = {https://hal.science/hal-05775817v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Transcriptional coupling of metabolism and cell mechanics controls human neuroepithelium morphogenesis
AU - Camil Mirdass
AU - Lucas Denis
AU - Hugo Lachuer
AU - Mikaëlle Bocel
AU - Anis Bourou
AU - Kamal Bouhali
AU - Nicolas Valentin
AU - Sandrine Adiba
AU - Alice Marteil
AU - Céline Chollet
AU - Emeline Chu-Van
AU - Xavier Baudin
AU - Catherine Pioche-Durieu
AU - Sarah Chebouti
AU - Bruno Estebe
AU - Frédéric Relaix
AU - Florence Castelli
AU - Valérie Dupe
AU - Sébastien Léon
AU - Stéphane Nedelec
AU - Nicolas Borghi
AU - Vanessa Ribes
PY - 2026
DA - 2026/09/22
PB - HAL
DO - 10.64898/2026.09.22.753382
UR - https://hal.science/hal-05775817v1
AB - Tissue morphogenesis integrates developmental programs with cell mechanics, yet the mechanisms coupling these processes remain poorly understood. We investigated this link during neuroepithelial morphogenesis in human iPSC-derived dorsal spinal organoids. We found that PAX3, a transcription factor whose loss causes neural tube defects, promotes force-bearing adherens junction assembly. It does so by driving apical clustering of N-cadherin complexes, thereby enabling neuroepithelial morphogenesis, a function conserved in the mouse neural tube. Transcriptomic, metabolomic, and functional analyses show that PAX3 sustains upper glycolysis and the associated mannose-dependent glycosylation pathways. Exogenous mannose rescues cadherin clustering and adherens junction mechanics following PAX3 loss, whereas inhibition of glycolysis or glycosylation recapitulates these defects. These findings establish mannose metabolism as a PAX3-regulated pathway conferring mechanical competence to developing tissues.
ER -