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| Status |
Public on Aug 31, 2020 |
| Title |
G-protein coupled receptor Gpr115 (Adgrf4) is required for enamel mineralization mediated by ameloblasts |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Dental enamel, the hardest tissue in the human body, is derived from dental epithelial cell ameloblast-secreted enamel matrices. Enamel mineralization occurs in a strictly synchronized manner along with ameloblast maturation in association with ion transport and pH balance, and any disruption of these processes results in enamel hypomineralization. G-protein coupled receptors (GPCRs) function as transducers of external signals by activating associated G-proteins and regulate cellular physiology. Tissue-specific GPCRs play important roles in organ development, though their activities in tooth development remains poorly understood. The present results show that the adhesion-GPCR Gpr115 (Adgrf4) is highly and preferentially expressed in mature ameloblasts and plays a crucial role during enamel mineralization. To investigate the in vivo function of Gpr115, knockout (Gpr115-KO) mice were created and found to develop hypo-mineralized enamel, with a larger acidic area due to the dysregulation of ion composition. Transcriptomic analysis also revealed that deletion of Gpr115 disrupted pH homeostasis and ion transport processes in enamel formation. In addition, in vitro analyses using the dental epithelial cell line Cervical Loop-Derived Dental Epithelial (CLDE) cell demonstrated that Gpr115 is indispensable for the expression of carbonic anhydrase 6 (Car6), which has a critical role in enamel mineralization. Furthermore, an acidic condition induced Car6 expression under the regulation of Gpr115 in CLDE cells. Thus, we concluded that Gpr115 plays an important role in enamel mineralization via regulation of Car6 expression in ameloblasts. The present findings indicate a novel function of Gpr115 in ectodermal organ development and clarify the molecular mechanism of enamel formation.
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| Overall design |
Tooth germ mRNA profiles of 7-day old wild type (WT) and Gpr115-/- mice were generated by RNA-sequencing, in triplicate, using Illumina Hiseq1500.
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| Contributor(s) |
Chiba Y, Yoshizaki K, Saito K, Ikeuchi T, Iwamoto T, Rhodes C, Nakamura T, de Vega S, Morell RJ, Boger ET, Martin D, Hino R, Inuzuka H, Bleck CK, Yamada A, Yamada Y, Fukumoto S |
| Citation(s) |
32868297 |
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| Submission date |
Aug 03, 2020 |
| Last update date |
Nov 30, 2020 |
| Contact name |
Yuta Chiba |
| E-mail(s) |
yuta.chiba.a8@tohoku.ac.jp
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| Phone |
810227178382
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| Organization name |
Tohoku University
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| Street address |
4-1 Seiryo-cho, Aoba-ku
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| City |
Sendai |
| State/province |
Miyagi |
| ZIP/Postal code |
980-0872 |
| Country |
Japan |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA650531 |
| SRA |
SRP275685 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155641_CPM_TMM_counts.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE155641_RawCountFile.txt.gz |
350.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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