The Evolutionary Young Actin Nucleator Cobl Is Important for Proper Amelogenesis

TL;DR

This study shows that the protein Cobl is important for the formation of tooth enamel by regulating the actin cytoskeleton in ameloblasts.

Contribution

The study identifies Cobl as a novel actin nucleator involved in amelogenesis and enamel composition.

Findings

Cobl is expressed in ameloblasts during the secretory phase of enamel formation.

Cobl influences ameloblast morphology, cytoskeletal organization, and enamel composition.

Cobl deficiency leads to altered F-actin content and increased enamel surface in mice.

Abstract

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, Cobl 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.

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