article published yes Yuuta Moriyama author addc9b8c-67a0-11f0-b374-a2e0948254700000-0002-2853-8051 Toshiyuki Mitsui author Carl-Philipp J Heisenberg author 39427864-F248-11E8-B48F-1D18A9856A870000-0002-0912-4566 CaHe department During embryonic development, cell behaviors need to be tightly regulated in time and space. Yet how the temporal and spatial regulations of cell behaviors are interconnected during embryonic development remains elusive. To address this, we turned to zebrafish gastrulation, the process whereby dynamic cell behaviors generate the three principal germ layers of the early embryo. Here, we show that Hoxb cluster genes are expressed in a temporally collinear manner at the blastoderm margin, where mesodermal and endodermal (mesendoderm) progenitor cells are specified and ingress to form mesendoderm/hypoblast. Functional analysis shows that these Hoxb genes regulate the timing of cell ingression: under- or overexpression of Hoxb genes perturb the timing of mesendoderm cell ingression and, consequently, the positioning of these cells along the forming anterior-posterior body axis after gastrulation. Finally, we found that Hoxb genes control the timing of mesendoderm ingression by regulating cellular bleb formation and cell surface fluctuations in the ingressing cells. Collectively, our findings suggest that Hoxb genes interconnect the temporal and spatial pattern of cell behaviors during zebrafish gastrulation by controlling cell surface fluctuations. https://research-explorer.ista.ac.at/download/20048/20070/2025_Development_Moriyama.pdf application/pdfno Company of Biologists2025 eng 0950-1991 1477-9129 40576478 00152525230000110.1242/dev.204261 15212 Y. Moriyama, T. Mitsui, C.-P.J. Heisenberg, Development 152 (2025). Moriyama Y, Mitsui T, Heisenberg C-PJ. 2025. Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation. Development. 152(12), dev204261. Moriyama, Yuuta, et al. “Hoxb Genes Determine the Timing of Cell Ingression by Regulating Cell Surface Fluctuations during Zebrafish Gastrulation.” <i>Development</i>, vol. 152, no. 12, dev204261, Company of Biologists, 2025, doi:<a href="https://doi.org/10.1242/dev.204261">10.1242/dev.204261</a>. Moriyama, Yuuta, Toshiyuki Mitsui, and Carl-Philipp J Heisenberg. “Hoxb Genes Determine the Timing of Cell Ingression by Regulating Cell Surface Fluctuations during Zebrafish Gastrulation.” <i>Development</i>. Company of Biologists, 2025. <a href="https://doi.org/10.1242/dev.204261">https://doi.org/10.1242/dev.204261</a>. Moriyama Y, Mitsui T, Heisenberg C-PJ. Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation. <i>Development</i>. 2025;152(12). doi:<a href="https://doi.org/10.1242/dev.204261">10.1242/dev.204261</a> Moriyama, Y., Mitsui, T., &#38; Heisenberg, C.-P. J. (2025). Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation. <i>Development</i>. Company of Biologists. <a href="https://doi.org/10.1242/dev.204261">https://doi.org/10.1242/dev.204261</a> Y. Moriyama, T. Mitsui, and C.-P. J. Heisenberg, “Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation,” <i>Development</i>, vol. 152, no. 12. Company of Biologists, 2025. 200482025-07-21T08:10:32Z2026-08-12T10:01:31Z