De La O Juana, Galea Gabriel L, Martin Adam C
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Department of Developmental Biology and Cancer Researching and Teaching, University College London Great Ormond Street Institute of Child Health, WC1N 1 EH London, United Kingdom.
bioRxiv. 2025 May 15:2025.05.15.654327. doi: 10.1101/2025.05.15.654327.
Organisms mold their tissues into increasingly more complicated shapes during development using a set of deformation motifs. One set of motifs are tissue hinges and creases which are created through cell-level shape changes. Hinges and creases are often made from active, anisotropic cell constriction at the hinge, which can help drive tissue folding. This contractile hinge model is observed in a variety of developmental tissue folding contexts, like during neural tube closure (NTC) of commonly studied species. However, patterns of cells constriction are inconsistent with this model, in the mouse brain. Additionally, formation of the midline neural tube hinge and crease are insensitive to the molecular machinery needed to induce cell shape changes. Here, we test if a contractile hinge is the driving mechanism for mouse cranial NTC. Through targeted laser ablations, we infer tissue tension in the folding mouse cranial neural tube. In contrast to predications of the contractile hinge model, we find the midline hinge has relatively low and isotropic tension, the lateral neural folds have higher anisotropic tension. We also show that regional patterns of tension vary by sex. We propose a lateral tension model for mouse cranial NTC and theorize on the connection between tissue mechanics and sex in NTC defects.
在发育过程中，生物体利用一系列变形模式将其组织塑造为越来越复杂的形状。其中一组模式是组织铰链和褶皱，它们是通过细胞水平的形状变化形成的。铰链和褶皱通常由铰链处活跃的、各向异性的细胞收缩形成，这有助于驱动组织折叠。这种收缩铰链模型在各种发育性组织折叠情况中都能观察到，比如在常见研究物种的神经管闭合（NTC）过程中。然而，在小鼠大脑中，细胞收缩模式与该模型不一致。此外，中线神经管铰链和褶皱的形成对诱导细胞形状变化所需的分子机制不敏感。在这里，我们测试收缩铰链是否是小鼠颅骨神经管闭合的驱动机制。通过靶向激光消融，我们推断正在折叠的小鼠颅骨神经管中的组织张力。与收缩铰链模型的预测相反，我们发现中线铰链具有相对较低且各向同性的张力，外侧神经褶具有较高的各向异性张力。我们还表明，张力的区域模式因性别而异。我们提出了一种小鼠颅骨神经管闭合的侧向张力模型，并对组织力学与神经管闭合缺陷中的性别之间的联系进行了理论探讨。
