JOURNAL OF CRANIOFACIAL SURGERY
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2017
·Vol. 28
·期 6
·1607-1614
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IF 0.788
Zhang Shixian,Wang Chengyong,Xie Changfu,Lai Yongzhen,Wu Di,Gan Guowu,Chen Weihui
The function of hedgehog signaling has previously been shown to be crucial for craniofacial development. In this study, we treated C57/BL6J mice with the hedgehog pathway inhibitor vismodegib by oral gavage to establish a stable vismodegib-induced cleft palate model.
At E10.5 and E12.5, mice in the experimental group were treated with 100 mg/kg of vismodegib, whereas mice in the control group were treated with solvent. The treated pregnant mice were sacrificed on E13.5, E14.5, E15.5, and E16.5. Palatal shelf growth was evaluated via histological and
immunohistochemical analyses as well as palatal organ culture. Immunohistochemical staining was performed to examine the expression of osteogenic proteins in the palatal tissue. A high proportion of the mice administered 2 doses of 100 mg/kg of vismodegib displayed a cleft palate. Histologic
examination revealed severely retarded palatal shelf growth and thickened epithelium in the experimental group. Vismodegib exposure induced complete cleft palate, which was attributed to a reduced cell proliferation rate in the palatal mesenchyme along the anterior-posterior axis. Moreover,
this model also showed delayed ossification in the region of palatine bone with downregulation of Indian hedgehog (Ihh) protein. Our results suggest that vismodegib can be used to inhibit hedgehog signaling to affect palatal morphogenesis. Under treatment with this exogenous inhibitor, the
cell proliferation rate of the palatal shelves and the osteogenic potential of the hard palate were decreased, which likely contributed to the complete cleft palate.
研究领域:
发育生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
·
2022
·Vol. 44
·期 2
·470-482
·
IF 2.976
Jiawang Tao,Yan Chen,Yuanqi Zhuang,Ruzhi Wei,Anteneh Getachew,Tingcai Pan,Fan Yang,Yinxiong Li
Liver regeneration is a complicated biological process orchestrated by various liver resident cells. Hepatic cell proliferation and reconstruction of the hepatic architecture involve multiple signaling pathways. It has been reported that the Hh signal is involved in liver regeneration. However, the signal transduction pathways and cell types involved are ill studied. This study aimed to investigate hedgehog signal response cell types and the specific molecular mechanism involved in the process of liver regeneration. Partial hepatectomy (PH) of 70% was performed on ICR (Institute of Cancer Research) mice to study the process of liver regeneration. We found that the hedgehog signal was activated significantly after PH, including hedgehog ligands, receptors and intracellular signaling molecules. Ligand signals were mainly expressed in bile duct cells and non-parenchymal hepatic cells, while receptors were expressed in hepatocytes and some non-parenchymal cells. Inhibition of the hedgehog signal treated with vismodegib reduced the liver regeneration rate after partial hepatectomy, including inhibition of hepatic cell proliferation by decreasing Cyclin D expression and disturbing the cell cycle through the accumulation of Cyclin B. The current study reveals the important role of the hedgehog signal and its participation in the regulation of hepatic cell proliferation and the cell cycle during liver regeneration. It provides new insight into the recovery of the liver after liver resection.Keywords:vismodegib;smoothened;liver regeneration;hedgehog signaling;mitosis
研究领域:
分子生物学
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细胞生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
DIFFERENTIATION
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2022
·
IF 3.533
Yan Guo,Di Wu,QingJiang Xu,Weihui Chen
The mandible is an important part of the craniofacial skeleton. Mandibular development is complex and involves multiple signaling pathways. These signaling pathways participate in a complex regulatory mechanism to regulate mandibular growth. The function of hedgehog signaling has previously been shown to be crucial for mandibular arch development. We treated pregnant ICR mice with the hedgehog pathway inhibitor vismodegib by oral gavage to establish a micrognathia model, which was mandible development defective. Compared to control, this model exhibited reduced mesenchymal cell proliferation and increased apoptosis. The development of the Meckel's cartilage and the condensations of mesenchymal cells were delayed by approximately one day in treated embryos. These results reveal that Smoothened may have shaped the mandible during mandibular growth by ensuring cell survival, proliferation, and development of Merkel's cartilage.
研究领域:
发育生物学
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分子生物学
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颅面研究
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DOI
PubMed
高影响因子
DEVELOPMENTAL DYNAMICS
·
2020
·Vol. 250
·期 4
·527-541
·
IF 3.275
Jiangping Chen,Wenbing Tang,Chengquan Lin,Yuhang Hong,Chuanqing Mao,Yongzhen Lai,Caiyu Liao,Minkui Lin,Weihui Chen
Background The hedgehog signaling pathway is critical for developmental patterning of the limb, craniofacial and axial skeleton. Disruption of this pathway in mice leads to a series of structural malformations, but the exact role and critical period of the Hh pathway in the early development of the cranial base have been rarely described. Results Embryos exposed to vismodegib from E7.5, E9.5, and E10.5 had a higher percentage of cranial base fenestra. The peak incidence of hypoplasia in sphenoid winglets and severe craniosynostosis in cranial base synchondroses was observed when vismodegib was administered between E9.5 and E10.5. Cranial base craniosynostosis results from accelerating terminal differentiation of chondrocytes and premature osteogenesis. Conclusions We define the critical periods for the induction of cranial base deformity by vismodegib administration at a meticulous temporal resolution. Our findings suggest that the Hh pathway may play a vital role in the early development of the cranial base. This research also establishes a novel and easy-to-establish mouse model of synostosis in the cranial base using a commercially available pathway-selective inhibitor.
研究领域:
发育生物学
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医学遗传学
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产品关联
DOI
PubMed
高影响因子
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