ISLET1-Dependent <i>β</i>-Catenin/Hedgehog Signaling Is Required for Outgrowth of the Lower Jaw

Li, Feixue; Fu, Guoquan; Liu, Ying; Miao, Xiaoping; Li, Yan; Yang, Xueqin; Zhang, Xiaoyun; Yu, Dongliang; Gan, Lin; Qiu, Mengsheng; Zhang, Ze; Zhang, Zunyi

doi:10.1128/mcb.00590-16

Cited by 19 publications

(20 citation statements)

References 49 publications

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“…To investigate the role of epidermal Wnt production in developmental regulation of tongue composition, we deleted Wls, the gene encoding the main regulator of Wnt protein trafficking, in the mandibular arch using an Shh-Cre mouse in which Cre is active in the dorsal epithelium of the tongue (24,27) (supplemental Fig. S1).…”

Section: Epithelial Wnt Production Is Essential For Embryonic Tongue mentioning

confidence: 99%

A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development

Zhu

Yuan

Wang

et al. 2017

Journal of Biological Chemistry

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The tongue is one of the major structures involved in human food intake and speech. Tongue malformations such as aglossia, microglossia, and ankyloglossia are congenital birth defects, greatly affecting individuals' quality of life. However, the molecular basis of the tissue-tissue interactions that ensure tissue morphogenesis to form a functional tongue remains largely unknown. Here we show that -mediated epithelial deletion of (), the key regulator for intracellular Wnt trafficking, leads to lingual hypoplasia in mice. Disruption of epithelial Wnt production by deletion in epithelial cells led to a failure in lingual epidermal stratification and loss of the lamina propria and the underlying superior longitudinal muscle in developing mouse tongues. These defective phenotypes resulted from a reduction in epithelial basal cells positive for the basal epidermal marker protein p63 and from impaired proliferation and differentiation in connective tissue and paired box 3 (Pax3)- and Pax7-positive muscle progenitor cells. We also found that epithelial Wnt production is required for activation of the Notch signaling pathway, which promotes proliferation of myogenic progenitor cells. Notch signaling in turn negatively regulated Wnt signaling during tongue morphogenesis. We further show that is a direct Notch target gene in the embryonic tongue. In summary, our findings demonstrate a key role for the lingual epithelial signals in supporting the integrity of the lamina propria and muscular tissue during tongue development and that a Wnt/Notch/Pax7 genetic hierarchy is involved in this development.

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Section: Epithelial Wnt Production Is Essential For Embryonic Tongue mentioning

confidence: 99%

A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development

Zhu

Yuan

Wang

et al. 2017

Journal of Biological Chemistry

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“…3). Among members of the Islet family, ISL1 is involved in the development of multiple tissues, including outgrowth of the lower jaw, as well as the patterning and mineralization of enamel (Li, Fu, et al 2017; Naveau et al 2017). The high sequence conservation between ISL1 and ISL2 suggests ISL2 might have a similar biological function.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide Analyses Identify a Novel Risk Locus for Nonsyndromic Cleft Palate

Zuo

Liu

et al. 2020

J Dent Res

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The 3 major subphenotypes observed in patients with nonsyndromic orofacial clefts (NSOFCs) are nonsyndromic cleft lip only (NSCLO), nonsyndromic cleft lip with palate (NSCLP), and nonsyndromic cleft palate only (NSCPO). However, the genetic architecture underlying NSCPO is largely unknown. Here we performed a 2-stage genome-wide association study (GWAS) on NSCPO and replication analyses of selected variants in other NSOFCs from the Chinese Han population. We identified a novel locus (15q24.3) and a known locus (1q32.2) where variants in or near the gene reached genome-wide significance (2.80 × 10−13 < P < 1.72 × 10−08) in a test for association with NSCPO in a case-control design. Although a variant from 15q24.3 was found to be significantly associated with both NSCPO and NSCLP, the direction of estimated effects on risk were opposite. Our functional annotation of the risk alleles within 15q24.3 coupled with previously established roles of the candidate genes within identified risk loci in periderm development, embryonic patterning, and/or regulation of cellular processes supports their involvement in palate development and the pathogenesis of cleft palate. Our study advances the understanding of the genetic basis of NSOFCs and provides novel insights into the pathogenesis of NSCPO.

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“…At the late stage of wound healing, TNF-α expression is mainly detected in osteoblasts and other mesenchymal cells [10,11], indicating that TNF-α actively participates in bone fracture regeneration [9]. Indeed, according to the literature data and our previous studies, a short-term exposure to low concentrations of TNF-α enhances the osteogenic differentiation of MSCs and osteoblasts, which in turn promotes bone regeneration [12][13][14][15] .…”

Section: Introductionmentioning

confidence: 90%

EphB4/ TNFR2/ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation

Zhang

Yang

et al. 2020

BMC Mol and Cell Biol

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Background: Low concentrations of tumor necrosis factor-alpha (TNF-α) and its receptor TNFR2 are both reported to promote osteogenic differentiation of osteoblast precursor cells. Moreover, low concentrations of TNF-α upregulate the expression of EphB4. However, the molecular mechanisms underlying TNF-α-induced osteogenic differentiation and the roles of TNFR2 and EphB4 have not been fully elucidated. Results: The ALP activity, as well as the mRNA and protein levels of RUNX2, BSP, EphB4 and TNFR2, was significantly elevated in MC3T3-E1 murine osteoblast precursor cells when stimulated with 0.5 ng/ml TNF-α. After TNFR2 was inhibited by gene knockdown with lentivirus-mediated shRNA interference or by a neutralizing antibody against TNFR2, the pro-osteogenic effect of TNF-α was partly reversed, while the up-regulation of EphB4 by TNF-α remained unchanged. With EphB4 forward signaling suppressed by a potent inhibitor of EphB4 auto-phosphorylation, NVP-BHG712, TNF-α-enhanced expressions of TNFR2, BSP and Runx2 were significantly decreased. Further investigation into the signaling pathways revealed that TNF-α significantly increased levels of p-JNK, pERK and p-p38. However, only the pERK level was significantly inhibited in TNFR2-knockdown cells. In addition, the ERK pathway inhibitor, U0126 (10 μM), significantly reversed the positive effect of TNF-α on the protein levels of RUNX2 and BSP. Conclusions: The EphB4, TNFR2 and ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation.

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ISLET1-Dependent β-Catenin/Hedgehog Signaling Is Required for Outgrowth of the Lower Jaw

Cited by 19 publications

References 49 publications

A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development

A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development

Genome-wide Analyses Identify a Novel Risk Locus for Nonsyndromic Cleft Palate

EphB4/ TNFR2/ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation

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