Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling

article Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling published yes Stefanie Rus author 4D9EC9B6-F248-11E8-B48F-1D18A9856A870000-0001-8703-1093 David Brückner author e1e86031-6537-11eb-953a-f7ab92be508d0000-0001-7205-2975 Thomas Minchington author 7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f Martina Greunz author 48A59534-F248-11E8-B48F-1D18A9856A87 Jack Merrin author 4515C308-F248-11E8-B48F-1D18A9856A870000-0001-5145-4609 Edouard B Hannezo author 3A9DB764-F248-11E8-B48F-1D18A9856A870000-0001-6005-1561 Anna Kicheva author 3959A2A0-F248-11E8-B48F-1D18A9856A870000-0003-4509-4998 AnKi department EdHa department NanoFab department Mechanisms of tissue size regulation in spinal cord development project Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord project The regulatory logic of pattern formation in the vertebrate dorsal neural tube project Developing tissues interpret dynamic changes in morphogen activity to generate cell type diversity. To quantitatively study bone morphogenetic protein (BMP) signaling dynamics in the mouse neural tube, we developed an embryonic stem cell differentiation system tailored for growing tissues. Differentiating cells form striking self-organized patterns of dorsal neural tube cell types driven by sequential phases of BMP signaling that are observed both in vitro and in vivo. Data-driven biophysical modeling showed that these dynamics result from coupling fast negative feedback with slow positive regulation of signaling by the specification of an endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling in space, we identify a BMP signaling relay that operates in time. This mechanism allows for a rapid initial concentration-sensitive response that is robustly terminated, thereby regulating balanced sequential cell type generation. Our study provides an experimental and theoretical framework to understand how signaling dynamics are exploited in developing tissues. https://research-explorer.ista.ac.at/download/18807/19584/2025_DevelopmentalCell_Lehr.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Elsevier2025 eng Developmental Cell 1534-5807 39603235 00143427900000110.1016/j.devcel.2024.10.024 604567-580 https://research-explorer.ista.ac.at/record/19763 S. Rus et al., “Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling,” Developmental Cell, vol. 60, no. 4. Elsevier, pp. 567–580, 2025. Rus, S., Brückner, D., Minchington, T., Greunz, M., Merrin, J., Hannezo, E. B., & Kicheva, A. (2025). Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. Developmental Cell. Elsevier. <a href="https://doi.org/10.1016/j.devcel.2024.10.024">https://doi.org/10.1016/j.devcel.2024.10.024</a> S. Rus, D. Brückner, T. Minchington, M. Greunz, J. Merrin, E.B. Hannezo, A. Kicheva, Developmental Cell 60 (2025) 567–580. Rus, Stefanie, et al. “Self-Organized Pattern Formation in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” Developmental Cell, vol. 60, no. 4, Elsevier, 2025, pp. 567–80, doi:<a href="https://doi.org/10.1016/j.devcel.2024.10.024">10.1016/j.devcel.2024.10.024</a>. Rus S, Brückner D, Minchington T, Greunz M, Merrin J, Hannezo EB, Kicheva A. 2025. Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. Developmental Cell. 60(4), 567–580. Rus, Stefanie, David Brückner, Thomas Minchington, Martina Greunz, Jack Merrin, Edouard B Hannezo, and Anna Kicheva. “Self-Organized Pattern Formation in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” Developmental Cell. Elsevier, 2025. <a href="https://doi.org/10.1016/j.devcel.2024.10.024">https://doi.org/10.1016/j.devcel.2024.10.024</a>. Rus S, Brückner D, Minchington T, et al. Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling. Developmental Cell. 2025;60(4):567-580. doi:<a href="https://doi.org/10.1016/j.devcel.2024.10.024">10.1016/j.devcel.2024.10.024</a> 188072025-01-09T11:25:47Z2026-10-09T22:31:15Z