Moriyama Yuuta, Mitsui Toshiyuki, Heisenberg Carl-Philipp
Institute of Science and Technology Austria, Am Campus 1, A-3400, Klosterneuburg, Austria.
Department of Physical Sciences, College of Science and Engineering, Aoyama Gakuin University, Kanagawa 252-5258, Japan.
Development. 2025 Jun 15;152(12). doi: 10.1242/dev.204261. Epub 2025 Jun 27.
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.
在胚胎发育过程中，细胞行为需要在时间和空间上受到严格调控。然而，在胚胎发育过程中，细胞行为的时间和空间调控是如何相互关联的，仍然不清楚。为了解决这个问题，我们转向斑马鱼原肠胚形成过程，在此过程中，动态的细胞行为产生了早期胚胎的三个主要胚层。在这里，我们表明Hoxb基因簇在胚盘边缘以时间共线性的方式表达，中胚层和内胚层（中内胚层）祖细胞在该位置被指定并内陷以形成中内胚层/下胚层。功能分析表明，这些Hoxb基因调节细胞内陷的时间：Hoxb基因的表达不足或过度表达会扰乱中内胚层细胞内陷的时间，从而影响原肠胚形成后这些细胞沿前后体轴的定位。最后，我们发现Hoxb基因通过调节内陷细胞中的细胞泡形成和细胞表面波动来控制中内胚层内陷的时间。总的来说，我们的研究结果表明，Hoxb基因通过控制细胞表面波动，在斑马鱼原肠胚形成过程中连接了细胞行为的时间和空间模式。
