دورية أكاديمية
Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition.
| العنوان: | Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. |
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| المؤلفون: | Krammer T; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030 Vienna, Austria., Stuart HT; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria; The Francis Crick Institute, London, UK., Gromberg E; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030 Vienna, Austria., Ishihara K; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria., Cislo D; Center for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA., Melchionda M; The Francis Crick Institute, London, UK., Becerril Perez F; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030 Vienna, Austria., Wang J; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria., Costantini E; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria., Lehr S; Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria., Arbanas L; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria., Hörmann A; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria., Neumüller RA; Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria., Elvassore N; Department of Industrial Engineering, University of Padova & Veneto Institute of Molecular Medicine (VIMM), Padova, Italy., Siggia E; Center for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA., Briscoe J; The Francis Crick Institute, London, UK., Kicheva A; Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria., Tanaka EM; Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria. Electronic address: elly.tanaka@imba.oeaw.ac.at. |
| المصدر: | Developmental cell [Dev Cell] 2024 Aug 05; Vol. 59 (15), pp. 1940-1953.e10. Date of Electronic Publication: 2024 May 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101120028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1551 (Electronic) Linking ISSN: 15345807 NLM ISO Abbreviation: Dev Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2001- |
| مواضيع طبية MeSH: | Organoids*/metabolism , Organoids*/cytology , Neural Tube*/metabolism , Neural Tube*/cytology , Notochord*/metabolism , Notochord*/cytology , Bone Morphogenetic Protein 4*/metabolism, Animals ; Mice ; Signal Transduction ; Hepatocyte Nuclear Factor 3-beta/metabolism ; Hepatocyte Nuclear Factor 3-beta/genetics ; Hedgehog Proteins/metabolism ; Hedgehog Proteins/genetics ; Carrier Proteins/metabolism ; Carrier Proteins/genetics ; Gene Expression Regulation, Developmental ; Bone Morphogenetic Proteins/metabolism |
| مستخلص: | During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable "winning" floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2 + clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering. Competing Interests: Declaration of interests A.H. and R.A.N. are full-time employees of Boehringer Ingelheim RCV. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: developmental biology; floorplate; neural tube; organoids; pattern formation; self-organization; stem cell differentiation; stem cells |
| المشرفين على المادة: | 148294-77-3 (noggin protein) 0 (Bone Morphogenetic Protein 4) 135845-92-0 (Hepatocyte Nuclear Factor 3-beta) 0 (Hedgehog Proteins) 0 (Foxa2 protein, mouse) 0 (Carrier Proteins) 0 (Bmp4 protein, mouse) 0 (Shh protein, mouse) 0 (Bone Morphogenetic Proteins) |
| تواريخ الأحداث: | Date Created: 20240522 Date Completed: 20240806 Latest Revision: 20240807 |
| رمز التحديث: | 20240808 |
| DOI: | 10.1016/j.devcel.2024.04.021 |
| PMID: | 38776925 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-1551 |
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| DOI: | 10.1016/j.devcel.2024.04.021 |