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Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation.

Wang SK, Hu Y, Yang J, Smith CE, Nunez SM, Richardson AS, Pal S, Samann AC, Hu JC, Simmer JP - Mol Genet Genomic Med (2015)

Bottom Line: The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle-ended ameloblasts.Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane.We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.

View Article: PubMed Central - PubMed

Affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Pl., Ann Arbor, Michigan, 48108.

ABSTRACT
Defects in WDR72 (WD repeat-containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72-knockout/lacZ-knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild-type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The enamel layer was only a tenth as hard as wild-type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin-associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle-ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.

No MeSH data available.


Related in: MedlinePlus

Backscattered SEMs of 7-week mouse mandibular first molars. The top panels show occlusal views; the middle panels show lingual views; the bottom panels show occlusal views. Although their basic morphologies stayed the same, all Wdr72−/− molars exhibited severe attrition, leaving blunted cusps and rough enamel surfaces.
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fig03: Backscattered SEMs of 7-week mouse mandibular first molars. The top panels show occlusal views; the middle panels show lingual views; the bottom panels show occlusal views. Although their basic morphologies stayed the same, all Wdr72−/− molars exhibited severe attrition, leaving blunted cusps and rough enamel surfaces.

Mentions: We examined the labial surfaces of 7-week mouse mandibular incisors by bSEM. The wild-type and heterozygous incisors had smooth enamel surfaces, while the enamel of incisors showed surface roughnesses unavoidably inflicted during soft tissue removal and due to severe attrition incisally (Fig. S5). Attrition was also observed on 7-week Wdr72−/− molars inspected by bSEM (Fig.3), which was not the case for the D14 (unerupted) molars that exhibited relatively normal crown size and shape (Fig.4).


Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation.

Wang SK, Hu Y, Yang J, Smith CE, Nunez SM, Richardson AS, Pal S, Samann AC, Hu JC, Simmer JP - Mol Genet Genomic Med (2015)

Backscattered SEMs of 7-week mouse mandibular first molars. The top panels show occlusal views; the middle panels show lingual views; the bottom panels show occlusal views. Although their basic morphologies stayed the same, all Wdr72−/− molars exhibited severe attrition, leaving blunted cusps and rough enamel surfaces.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4521966&req=5

fig03: Backscattered SEMs of 7-week mouse mandibular first molars. The top panels show occlusal views; the middle panels show lingual views; the bottom panels show occlusal views. Although their basic morphologies stayed the same, all Wdr72−/− molars exhibited severe attrition, leaving blunted cusps and rough enamel surfaces.
Mentions: We examined the labial surfaces of 7-week mouse mandibular incisors by bSEM. The wild-type and heterozygous incisors had smooth enamel surfaces, while the enamel of incisors showed surface roughnesses unavoidably inflicted during soft tissue removal and due to severe attrition incisally (Fig. S5). Attrition was also observed on 7-week Wdr72−/− molars inspected by bSEM (Fig.3), which was not the case for the D14 (unerupted) molars that exhibited relatively normal crown size and shape (Fig.4).

Bottom Line: The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle-ended ameloblasts.Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane.We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.

View Article: PubMed Central - PubMed

Affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry 1210 Eisenhower Pl., Ann Arbor, Michigan, 48108.

ABSTRACT
Defects in WDR72 (WD repeat-containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72-knockout/lacZ-knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild-type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The enamel layer was only a tenth as hard as wild-type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin-associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle-ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.

No MeSH data available.


Related in: MedlinePlus