Profiles of Wnt pathway gene expression during tooth morphogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE247224 | GEO | 2023/11/22
REPOSITORIES: GEO
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Project description: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. 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.
2013-01-22 | E-GEOD-39918 | biostudies-arrayexpress
Project description: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.
2013-01-22 | GSE39918 | GEO
Project description:One of the key questions in developmental biology is how from universally shared molecular mechanisms and pathways, is it possible to generate organs displaying similar or complementary functions, with a wide range of different shapes or tissue organization? The dentition represents a valuable system to address the issues of differential molecular signatures generating specific tooth types. We performed a comparative transcriptomic analysis of developing murine lower incisors, mandibular molars and maxillary molars at the developmental cap stage (E14.5) prior to recognizable tooth shape and cusp pattern. We compared gene expression profiles in developing murine lower incisor and molars, as well as between the lower and upper (mandibular and maxillary) first molars
2013-03-31 | E-GEOD-43144 | biostudies-arrayexpress
Project description:Mutations in MSX1 cause craniofacial developmental defects, including tooth agenesis, in humans and mice. Previous studies suggest that Msx1 activates Bmp4 expression in the developing tooth mesenchyme to drive early tooth organogenesis. Whereas Msx1−/− mice exhibit developmental arrest of all tooth germs at the bud stage, however, mice with neural crest-specific inactivation of Bmp4 (Bmp4ncko/ncko), which lack Bmp4 expression in the developing tooth mesenchyme, showed developmental arrest of only mandibular molars. We recently demonstrated that deletion of Osr2, which encodes a zinc finger transcription factor expressed in a lingual-to-buccal gradient in the developing tooth bud mesenchyme, rescued molar tooth morphogenesis in both Msx1−/− and Bmp4ncko/ncko mice. In this study, through RNA-seq analyses of the developing tooth mesenchyme in mutant and wildtype embryos, we found that Msx1 and Osr2 have opposite effects on expression of several secreted Wnt antagonists in the tooth bud mesenchyme. Remarkably, both Dkk2 and Sfrp2 exhibit Osr2-dependent preferential expression on the lingual side of the tooth bud mesenchyme and expression of both genes was up-regulated and expanded into the tooth bud mesenchyme in Msx1−/− and Bmp4ncko/ncko mutant embryos. We show that pharmacological activation of canonical Wnt signaling by either lithium chloride (LiCl) treatment or by inhibition of Dkk in utero was sufficient to rescue mandibular molar tooth morphogenesis in Bmp4ncko/ncko mice. Furthermore, whereas inhibition of Dkk alone was insufficient to rescue tooth morphogenesis in Msx1−/− mice, pharmacological inhibition of Dkk in combination with genetic inactivation of Sfrp2 and Sfrp3 rescued maxillary molar morphogenesis in Msx1−/− mice. Together, these data reveal a novel mechanism that the Bmp4-Msx1 pathway drives tooth organogenesis by activating Wnt signaling via regulation of the secreted Wnt antagonists.
2017-05-12 | GSE81282 | GEO
Project description:Mutations in MSX1 cause craniofacial developmental defects, including tooth agenesis, in humans and mice. Previous studies suggest that Msx1 activates Bmp4 expression in the developing tooth mesenchyme to drive early tooth organogenesis. Whereas Msx1−/− mice exhibit developmental arrest of all tooth germs at the bud stage, however, mice with neural crest-specific inactivation of Bmp4 (Bmp4ncko/ncko), which lack Bmp4 expression in the developing tooth mesenchyme, showed developmental arrest of only mandibular molars. We recently demonstrated that deletion of Osr2, which encodes a zinc finger transcription factor expressed in a lingual-to-buccal gradient in the developing tooth bud mesenchyme, rescued molar tooth morphogenesis in both Msx1−/− and Bmp4ncko/ncko mice. In this study, through RNA-seq analyses of the developing tooth mesenchyme in mutant and wildtype embryos, we found that Msx1 and Osr2 have opposite effects on expression of several secreted Wnt antagonists in the tooth bud mesenchyme. Remarkably, both Dkk2 and Sfrp2 exhibit Osr2-dependent preferential expression on the lingual side of the tooth bud mesenchyme and expression of both genes was up-regulated and expanded into the tooth bud mesenchyme in Msx1−/− and Bmp4ncko/ncko mutant embryos. We show that pharmacological activation of canonical Wnt signaling by either lithium chloride (LiCl) treatment or by inhibition of Dkk in utero was sufficient to rescue mandibular molar tooth morphogenesis in Bmp4ncko/ncko mice. Furthermore, whereas inhibition of Dkk alone was insufficient to rescue tooth morphogenesis in Msx1−/− mice, pharmacological inhibition of Dkk in combination with genetic inactivation of Sfrp2 and Sfrp3 rescued maxillary molar morphogenesis in Msx1−/− mice. Together, these data reveal a novel mechanism that the Bmp4-Msx1 pathway drives tooth organogenesis by activating Wnt signaling via regulation of the secreted Wnt antagonists.
2017-05-11 | GSE80288 | GEO
Project description:One of the key questions in developmental biology is how from universally shared molecular mechanisms and pathways, is it possible to generate organs displaying similar or complementary functions, with a wide range of different shapes or tissue organization? The dentition represents a valuable system to address the issues of differential molecular signatures generating specific tooth types. We performed a comparative transcriptomic analysis of developing murine lower incisors, mandibular molars and maxillary molars at the developmental cap stage (E14.5) prior to recognizable tooth shape and cusp pattern.
2013-03-31 | GSE43144 | GEO
Project description:Gene expression profiles were generated from embryonic day 13.5 CD-1 mouse mandibular first molars whole tooth and non-tooth non-bone oral tissue.
2012-10-06 | GSE41380 | GEO
Project description:Gene expression profiles were generated from embryonic day 13.5 CD-1 mouse mandibular first molars whole tooth and non-tooth non-bone oral tissue. Three biological replicates from embryonic day 13.5 CD-1 mice were generated from pooled tissues across multiple mice. The tooth germ and non-tooth oral tissues were paired from the same embryos.
2012-10-06 | E-GEOD-41380 | biostudies-arrayexpress
Project description:How the dorsal-ventral axis of the vertebrate jaw, particularly the position of tooth initiation site, is established remains a critical and unresolved question. Tooth development starts with the formation of the dental lamina, a localized thickened strip within the maxillary and mandibular epithelium. To identify transcriptional regulatory networks (TRN) controlling the specification of dental lamina from the naïve mandibular epithelium, we utilized Laser Microdissection coupled low-input RNA-seq (LMD-RNA-seq) to profile gene expression of different domains of the mandibular epithelium along the dorsal-ventral axis in wild type mouse and two loss-of-function mouse models of domain specific transcription factors.
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Project description:Study of changes in gene expression in mouse tooth germs between E15.5 and 21.5dpc
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