Janitzek Hannes, González Delgado Jule, Haag Natja, Seemann Eric, Nietzsche Sandor, Sigusch Bernd, Qualmann Britta, Kessels Michael Manfred
Institute of Biochemistry I, Jena University Hospital-Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, Germany.
Center for Electron Microscopy, Jena University Hospital-Friedrich Schiller University Jena, Ziegelmühlenweg 1, 07743 Jena, Germany.
Cells. 2025 Feb 28;14(5):359. doi: 10.3390/cells14050359.
The actin cytoskeleton plays an important role in morphological changes of ameloblasts during the formation of enamel, which is indispensable for teeth to withstand wear, fracture and caries progression. This study reveals that the actin nucleator Cobl is expressed in ameloblasts of mandibular molars during amelogenesis. Cobl expression was particularly pronounced during the secretory phase of the enamel-forming cells. Cobl colocalized with actin filaments at the cell cortex. Importantly, our analyses show an influence of Cobl on both ameloblast morphology and cytoskeletal organization as well as on enamel composition. At P0, knock-out causes an increased height of ameloblasts and an increased F-actin content at the apical membrane. During the maturation phase, the F-actin density at the apical membrane was instead significantly reduced when compared to WT mice. At the same time, Cobl-deficient mice showed an increased carbon content of the enamel and an increased enamel surface of mandibular molars. These findings demonstrate a decisive influence of the actin nucleator Cobl on the actin cytoskeleton and the morphology of ameloblasts during amelogenesis. Our work thus expands the understanding of the regulation of the actin cytoskeleton during amelogenesis and helps to further elucidate the complex processes of enamel formation during tooth development.
肌动蛋白细胞骨架在釉质形成过程中对成釉细胞的形态变化起重要作用，而釉质对于牙齿抵抗磨损、断裂和龋齿进展是不可或缺的。本研究表明，肌动蛋白成核因子Cobl在成釉细胞生成过程中在下颌磨牙的成釉细胞中表达。Cobl的表达在釉质形成细胞的分泌期尤为明显。Cobl与细胞皮质处的肌动蛋白丝共定位。重要的是，我们的分析表明Cobl对成釉细胞形态和细胞骨架组织以及釉质成分均有影响。在出生后第0天，基因敲除导致成釉细胞高度增加以及顶端膜处F-肌动蛋白含量增加。在成熟阶段，与野生型小鼠相比，顶端膜处的F-肌动蛋白密度反而显著降低。同时，Cobl缺陷型小鼠的釉质碳含量增加，下颌磨牙的釉质表面积增加。这些发现证明了肌动蛋白成核因子Cobl在成釉细胞生成过程中对肌动蛋白细胞骨架和成釉细胞形态具有决定性影响。因此，我们的工作扩展了对成釉细胞生成过程中肌动蛋白细胞骨架调节的理解，并有助于进一步阐明牙齿发育过程中釉质形成的复杂过程。
