Zhao Zhiling, Asai Rieko, Mikawa Takashi
Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, California, USA.
Dev Dyn. 2025 Jun 12. doi: 10.1002/dvdy.70045.
Midline establishment is a fundamental process during early embryogenesis for Bilaterians. Midline morphogenesis in non-amniotes can occur without mitosis, through Planar Cell Polarity (PCP) signaling. By contrast, amniotes utilize both cellular processes for developing the early midline landmark, the primitive streak (PS). This study focused on the role of cell proliferation for midline development at pre- and post-PS-extension stages and analyzed PCP signaling components at post-PS-extension stages.
In contrast to pre-PS-extension stages, embryos under mitotic arrest during the post-PS-extension preserved notochord (NC) extension and Hensen's node (HN)/PS regression judged by both morphology and marker genes; although they became shorter, their lengths remained proportional to the embryo length. Laterality and segmentation of paraxial mesoderm were lost upon mitotic arrest. Accompanied by mitotic arrest-induced embryonic size reduction, cells including midline tissue displayed hypertrophy.
This study has identified at least two distinct mitosis sensitivity phases during early midline development: One is PS extension that requires both mitosis and PCP, and the other is mitotic arrest-resistant midline development at post-PS-extension stages, with a still undefined influence by PCP signaling components.
中线确立是两侧对称动物早期胚胎发育过程中的一个基本过程。非羊膜动物的中线形态发生可在无有丝分裂的情况下通过平面细胞极性(PCP)信号传导发生。相比之下,羊膜动物利用这两种细胞过程来发育早期中线标志——原条(PS)。本研究聚焦于细胞增殖在原条延伸前和延伸后阶段中线发育中的作用,并分析了原条延伸后阶段的PCP信号成分。
与原条延伸前阶段不同,在原条延伸后处于有丝分裂阻滞状态的胚胎,根据形态学和标记基因判断,保留了脊索(NC)延伸和亨氏结(HN)/原条退化;尽管它们变短了,但其长度仍与胚胎长度成比例。有丝分裂阻滞时,轴旁中胚层的左右不对称和分节消失。伴随着有丝分裂阻滞导致的胚胎大小减小,包括中线组织在内的细胞出现肥大。
本研究确定了早期中线发育过程中至少两个不同的有丝分裂敏感阶段:一个是原条延伸阶段,这需要有丝分裂和PCP信号;另一个是原条延伸后阶段对有丝分裂阻滞有抗性的中线发育阶段,PCP信号成分对其影响尚不清楚。