article published yes Teresa Krammer author Hannah T. Stuart author Elena Gromberg author Keisuke Ishihara author Dillon Cislo author Manuela Melchionda author Fernando Becerril Perez author Jingkui Wang author Elena Costantini author Stefanie Rus author 4D9EC9B6-F248-11E8-B48F-1D18A9856A870000-0001-8703-1093 Laura Arbanas author Alexandra Hörmann author Ralph A. Neumüller author Nicola Elvassore author Eric Siggia author James Briscoe author Anna Kicheva author 3959A2A0-F248-11E8-B48F-1D18A9856A870000-0003-4509-4998 Elly M. Tanaka author AnKi department Mechanisms of tissue size regulation in spinal cord development project The regulatory logic of pattern formation in the vertebrate dorsal neural tube project 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. https://research-explorer.ista.ac.at/download/17148/18841/2024_DevelopmentalCell_Krammer.pdf application/pdfno https://creativecommons.org/licenses/by-nc-nd/4.0/ Elsevier2024 eng 1534-5807 1878-1551 38776925 00128968480000110.1016/j.devcel.2024.04.021 59151940-1953.e10 https://research-explorer.ista.ac.at/record/19763 Krammer T, Stuart HT, Gromberg E, et al. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. <i>Developmental Cell</i>. 2024;59(15):1940-1953.e10. doi:<a href="https://doi.org/10.1016/j.devcel.2024.04.021">10.1016/j.devcel.2024.04.021</a> Krammer T, Stuart HT, Gromberg E, Ishihara K, Cislo D, Melchionda M, Becerril Perez F, Wang J, Costantini E, Rus S, Arbanas L, Hörmann A, Neumüller RA, Elvassore N, Siggia E, Briscoe J, Kicheva A, Tanaka EM. 2024. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell. 59(15), 1940–1953.e10. Krammer, Teresa, Hannah T. Stuart, Elena Gromberg, Keisuke Ishihara, Dillon Cislo, Manuela Melchionda, Fernando Becerril Perez, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” <i>Developmental Cell</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.devcel.2024.04.021">https://doi.org/10.1016/j.devcel.2024.04.021</a>. Krammer, Teresa, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” <i>Developmental Cell</i>, vol. 59, no. 15, Elsevier, 2024, p. 1940–1953.e10, doi:<a href="https://doi.org/10.1016/j.devcel.2024.04.021">10.1016/j.devcel.2024.04.021</a>. Krammer, T., Stuart, H. T., Gromberg, E., Ishihara, K., Cislo, D., Melchionda, M., … Tanaka, E. M. (2024). Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. <i>Developmental Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.devcel.2024.04.021">https://doi.org/10.1016/j.devcel.2024.04.021</a> T. Krammer, H.T. Stuart, E. Gromberg, K. Ishihara, D. Cislo, M. Melchionda, F. Becerril Perez, J. Wang, E. Costantini, S. Rus, L. Arbanas, A. Hörmann, R.A. Neumüller, N. Elvassore, E. Siggia, J. Briscoe, A. Kicheva, E.M. Tanaka, Developmental Cell 59 (2024) 1940–1953.e10. T. Krammer <i>et al.</i>, “Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition,” <i>Developmental Cell</i>, vol. 59, no. 15. Elsevier, p. 1940–1953.e10, 2024. 171482024-06-16T22:01:07Z2026-07-11T22:30:28Z