ArticleProceedings of the National Academy of Sciences of the United States of America2022
Temporal changes in plasma membrane lipid content induce endocytosis to regulate developmental epithelial-to-mesenchymal transition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 18 citations in OpenAlex.
- The lipid raft-linker gene Raftlin-2 is expressed in migrating neural crest cells.Differentiation; research in biological diversity · 2026Article
- Development of a FRET-Based Assay for Human Neutral Sphingomyelinase 2.Biochemistry · 2026Article
- C-terminal interleukin 1 alpha (IL-1α) overexpression drives EMT and a vulnerability to ferroptosis in HNSCC.Redox biology · 2026Article
- Behind the membranous curtain-lipid dynamics and functions in coronaviral replication.Journal of virology · 2026Review
- Extracellular Vesicles fromNanomaterials (Basel, Switzerland) · 2026Article
- Unconventional Secretion of Angiogenic Sonic Hedgehog-Containing Extra-Large Extracellular Vesicles is Driven by PI3K-Rab18-GDP Signalling.Journal of extracellular biology · 2026Article
- Lipid-mediated reinforcement of FGF/MAPK signaling enables robust otic placode specification.bioRxiv : the preprint server for biology · 2026Article
- Assessing the Nature of Human Brain-Derived Extracellular Vesicles on Synaptic Activity Via the Development of an Air-liquid Microfluidic Platform.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- SMPD3 expression is spatially regulated in the developing embryo by SOXE factors.Developmental biology · 2024Article
- "Beyond transcription: How post-transcriptional mechanisms drive neural crest EMT".Genesis (New York, N.Y. : 2000) · 2024Review
- Reprogrammed lipid metabolism in advanced resistant cancers: an upcoming therapeutic opportunity.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- A suitable model to investigate acute neurological consequences of coronavirus infection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β-catenin signaling and tumor growth.Molecular oncology · 2023Article
- Time to go: neural crest cell epithelial-to-mesenchymal transition.Development (Cambridge, England) · 2022Review
- Essential function and targets of BMP signaling during midbrain neural crest delamination.Developmental biology · 2021Article
- Transcriptomic Identification of Draxin-Responsive Targets During Cranial Neural Crest EMT.Frontiers in physiology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Epithelial-to-mesenchymal transition (EMT) is a dramatic change in cellular physiology during development and metastasis, which requires coordination between cell signaling, adhesion, and membrane protrusions. These processes all involve dynamic changes in the plasma membrane; yet, how membrane lipid content regulates membrane function during EMT remains incompletely understood. By screening for differential expression of lipid-modifying genes over the course of EMT in the avian neural crest, we have identified the ceramide-producing enzyme neutral sphingomyelinase 2 (nSMase2) as a critical regulator of a developmental EMT. nSMase2 expression begins at the onset of EMT, and in vivo knockdown experiments demonstrate that nSMase2 is necessary for neural crest migration. We find that nSMase2 promotes Wnt and BMP signaling and is required to activate the mesenchymal gene expression program. Mechanistically, we show that nSMase2-dependent ceramide production is necessary for and sufficient to up-regulate endocytosis and is required for Wnt co-receptor internalization. Finally, inhibition of endocytosis in the neural crest mimics the loss of migration and Wnt signaling observed following nSMase2 knockdown. Our results support a model in which nSMase2 is expressed at the onset of neural crest EMT to produce ceramide and facilitate receptor-mediated endocytosis of Wnt and BMP signaling complexes, thereby activating promigratory gene expression. These results highlight the critical role of plasma membrane lipid metabolism in regulating transcriptional changes during developmental EMT programs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.