Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development
Abstract Metabolic reprograming has been linked to epithelial-to-mesenchymal transition (EMT) in cancer cells, but how it influences EMT in normal cells remains largely unknown. Here we explored how metabolism impacts delamination and migration of avian trunk neural crest cells, an important progeni...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58573-0 |
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| author | Nioosha Nekooie Marnany Alwyn Dady Isabelle Duband-Goulet Frédéric Relaix Roberto Motterlini Roberta Foresti Sylvie Dufour Jean-Loup Duband |
| author_facet | Nioosha Nekooie Marnany Alwyn Dady Isabelle Duband-Goulet Frédéric Relaix Roberto Motterlini Roberta Foresti Sylvie Dufour Jean-Loup Duband |
| author_sort | Nioosha Nekooie Marnany |
| collection | DOAJ |
| description | Abstract Metabolic reprograming has been linked to epithelial-to-mesenchymal transition (EMT) in cancer cells, but how it influences EMT in normal cells remains largely unknown. Here we explored how metabolism impacts delamination and migration of avian trunk neural crest cells, an important progenitor cell population of the vertebrate embryo. We report that delamination exhibits a quiescent metabolic phenotype whereas migration is characterized by OXPHOS-driven metabolism coupled to distinct expression of metabolic, EMT and developmental genes. While glucose and glutamine are required for delamination and migration, we uncover a specific role for glutamine and its catabolizing enzyme glutaminase in the unfolding of NCC delamination. Namely, glutamine is required for nuclear accumulation of glutaminase, which interacts and cooperates with Wnt signaling to regulate EMT gene expression and cell cycle during delamination. Our data indicate that similarly to cancer cells, embryonic cells engage metabolic enzymes for non-canonical signaling functions to connect metabolism with EMT. |
| format | Article |
| id | doaj-art-1c32e2d794e8430b99c9acd7fafad276 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1c32e2d794e8430b99c9acd7fafad2762025-08-20T03:03:34ZengNature PortfolioNature Communications2041-17232025-07-0116112210.1038/s41467-025-58573-0Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest developmentNioosha Nekooie Marnany0Alwyn Dady1Isabelle Duband-Goulet2Frédéric Relaix3Roberto Motterlini4Roberta Foresti5Sylvie Dufour6Jean-Loup Duband7Institut Mondor de Recherches Biomédicales, Faculté de Santé, INSERM, Université Paris-Est CréteilLaboratoire Gly-CRRET, Université Paris-Est CréteilLaboratoire de Myologie Fondamentale et Translationnelle, CNRS, Université Paris CitéInstitut Mondor de Recherches Biomédicales, Faculté de Santé, INSERM, Université Paris-Est CréteilInstitut Mondor de Recherches Biomédicales, Faculté de Santé, INSERM, Université Paris-Est CréteilInstitut Mondor de Recherches Biomédicales, Faculté de Santé, INSERM, Université Paris-Est CréteilInstitut Mondor de Recherches Biomédicales, Faculté de Santé, INSERM, Université Paris-Est CréteilInstitut Mondor de Recherches Biomédicales, Faculté de Santé, INSERM, Université Paris-Est CréteilAbstract Metabolic reprograming has been linked to epithelial-to-mesenchymal transition (EMT) in cancer cells, but how it influences EMT in normal cells remains largely unknown. Here we explored how metabolism impacts delamination and migration of avian trunk neural crest cells, an important progenitor cell population of the vertebrate embryo. We report that delamination exhibits a quiescent metabolic phenotype whereas migration is characterized by OXPHOS-driven metabolism coupled to distinct expression of metabolic, EMT and developmental genes. While glucose and glutamine are required for delamination and migration, we uncover a specific role for glutamine and its catabolizing enzyme glutaminase in the unfolding of NCC delamination. Namely, glutamine is required for nuclear accumulation of glutaminase, which interacts and cooperates with Wnt signaling to regulate EMT gene expression and cell cycle during delamination. Our data indicate that similarly to cancer cells, embryonic cells engage metabolic enzymes for non-canonical signaling functions to connect metabolism with EMT.https://doi.org/10.1038/s41467-025-58573-0 |
| spellingShingle | Nioosha Nekooie Marnany Alwyn Dady Isabelle Duband-Goulet Frédéric Relaix Roberto Motterlini Roberta Foresti Sylvie Dufour Jean-Loup Duband Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development Nature Communications |
| title | Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development |
| title_full | Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development |
| title_fullStr | Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development |
| title_full_unstemmed | Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development |
| title_short | Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development |
| title_sort | non canonical nuclear function of glutaminase cooperates with wnt signaling to drive emt during neural crest development |
| url | https://doi.org/10.1038/s41467-025-58573-0 |
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