Umar Meenakshi, Bartoletti Garrett, Sokolowskei Dimitri, Janser Nathan, Tower Robert, He Fenglei
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA.
Res Sq. 2025 Aug 5:rs.3.rs-7216722. doi: 10.21203/rs.3.rs-7216722/v1.
Craniosynostosis is a congenital defect characterized by the premature fusion of calvarial bones, often attributed to the loss of fibrous sutures or deregulated bone formation. Recent studies have reported abnormal cartilage formation in multiple synostosis models, suggesting a potential role for cartilage in suture formation and maintenance. The tectum transversum (TTR) is a transient cartilage located between the coronal suture and dura, adjacent to the frontal and parietal bones. Abnormal TTR formation has been observed in several models; however, its role in coronal suture development remains unclear. In this study, we investigated the developmental process of TTR in a mouse model and characterized its formation in relation to adjacent tissues, including the calvarial bones and the coronal suture. Through genetic ablation of TTR, we demonstrated its essential role in maintaining coronal suture patency. Furthermore, spatial transcriptomics data suggest that TTR may function as a barrier to BMP signaling activation in the coronal suture, a process potentially influenced by the dura. These findings provide new insights into the mechanisms regulating coronal suture development and the etiology of coronal synostosis.
颅缝早闭是一种先天性缺陷，其特征为颅骨过早融合，通常归因于纤维性骨缝的缺失或骨形成失调。最近的研究报道了在多种颅缝早闭模型中存在异常软骨形成，提示软骨在骨缝形成和维持中可能发挥作用。横枕骨（TTR）是位于冠状缝和硬脑膜之间、毗邻额骨和顶骨的一种临时性软骨。在多个模型中均观察到TTR形成异常；然而，其在冠状缝发育中的作用仍不明确。在本研究中，我们在小鼠模型中研究了TTR的发育过程，并描述了其与包括颅骨和冠状缝在内的相邻组织相关的形成情况。通过对TTR进行基因敲除，我们证明了其在维持冠状缝通畅方面的重要作用。此外，空间转录组学数据表明，TTR可能作为冠状缝中骨形态发生蛋白（BMP）信号激活的屏障，这一过程可能受硬脑膜影响。这些发现为调控冠状缝发育的机制及冠状缝早闭的病因提供了新的见解。
