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Series GSE39918 Query DataSets for GSE39918
Status Public on Jan 22, 2013
Title Next-generation sequencing facilitates quantitative analysis of wild type and Bmp4f/f;Wnt1Cre tooth mesenchyme transcriptomes
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Previous studies have suggested that Bmp4 is a key Msx1-dependent mesenchymal odontogenic signal for driving tooth morphogenesis through the bud-to-cap transition. Whereas the bud stage tooth developmental arrest in Msx1-/- mutant mice was accompanied by reduction in mesenchymal Bmp4 mRNA expression, we show that depleting functional Bmp4 mRNAs in the tooth mesenchyme, through neural crest-specific gene inactivation in Bmp4f/f;Wnt1Cre mice, caused mandibular molar developmental arrest at the bud stage but allowed maxillary molars and incisors to develop to mineralized teeth. We show that the Wnt inhibitors Dkk2 and Wif1 were much more abundantly expressed in the mandibular than maxillary molar mesenchyme in wildtype embryos and that Dkk2 expression was significantly unregulated in the tooth mesenchyme in Bmp4f/f;Wnt1Cre embryos. In addition, expression of Osr2, which encodes a zinc finger protein that antagonizes Msx1-mediated activation of odontogenic mesenchyme, is significantly upregulated in the molar mesenchyme in Bmp4f/f;Wnt1Cre embryos. Msx1 heterozygosity enhanced maxillary molar developmental defects whereas Osr2 heterozygosity rescued mandibular first molar morphogenesis in Bmp4f/f;Wnt1Cre mice. Moreover, in contrast to complete lack of supernumerary tooth initiation in Msx1-/-Osr2-/- mutant mice, Osr2-/-Bmp4f/f;Wnt1Cre compound mutant mice exhibit formation and subsequent arrest of supernumerary tooth germs that correlated with down regulation of Msx1 expression in the tooth mesenchyme. Taken together, our data indicate that, while reduction in mesenchymal Bmp4 expression alone could not account for the tooth bud arrest phenotype in Msx1-/- mutant mice, Bmp4 signaling synergizes with Msx1 and antagonizes Osr2 to activate mesenchymal odontogenic activity to drive tooth morphogenesis and sequential tooth formation.
Overall design E13.5 mouse embryos tooth germs were microdissected by laser capture microdissection (LCM), and the mandibular molar and maxillary molar were separated. 3 pairs of control and mutant samples were pooled for the RNA extraction.
Contributor(s) Jiang R, Jia S
Citation(s) 23250216
Submission date Aug 06, 2012
Last update date May 15, 2019
Contact name Shihai Jia
Organization name Cincinnati Children's Hospital Medical Center
Department Division of Developmental Biology
Lab Rulang Jiang
Street address 3333 Burnet Ave
City Cincinnati
State/province Ohio
ZIP/Postal code 45229
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM981302 Bmp4f/+ upper molar
GSM981303 Bmp4f/+ lower molar
GSM981304 Bmp4f/f;Wnt1Cre upper molar
BioProject PRJNA172025
SRA SRP014717

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Supplementary file Size Download File type/resource
GSE39918_RAW.tar 2.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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