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CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation

BACKGROUND: CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme...

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Autores principales: Zhou, Tao, Chen, Guoqing, Xu, Yuchan, Zhang, Shuning, Tang, Huilin, Qiu, Tao, Guo, Weihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510226/
https://www.ncbi.nlm.nih.gov/pubmed/37726858
http://dx.doi.org/10.1186/s13287-023-03486-2
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author Zhou, Tao
Chen, Guoqing
Xu, Yuchan
Zhang, Shuning
Tang, Huilin
Qiu, Tao
Guo, Weihua
author_facet Zhou, Tao
Chen, Guoqing
Xu, Yuchan
Zhang, Shuning
Tang, Huilin
Qiu, Tao
Guo, Weihua
author_sort Zhou, Tao
collection PubMed
description BACKGROUND: CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation. METHODS: The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig’s epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket. RESULTS: CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn’t disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/β-catenin signaling as the downstream target of CDC42 modulated DPCs’ odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs. CONCLUSIONS: We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03486-2.
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spelling pubmed-105102262023-09-21 CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation Zhou, Tao Chen, Guoqing Xu, Yuchan Zhang, Shuning Tang, Huilin Qiu, Tao Guo, Weihua Stem Cell Res Ther Research BACKGROUND: CDC42 is a member of Rho GTPase family, acting as a molecular switch to regulate cytoskeleton organization and junction maturation of epithelium in organ development. Tooth root pattern is a highly complicated and dynamic process that dependens on interaction of epithelium and mesenchyme. However, there is a lack of understanding of the role of CDC42 during tooth root elongation. METHODS: The dynamic expression of CDC42 was traced during tooth development through immunofluorescence staining. Then we constructed a model of lentivirus or inhibitor mediated Cdc42 knockdown in Herwig’s epithelial root sheath (HERS) cells and dental papilla cells (DPCs), respectively. Long-term influence of CDC42 abnormality was assessed via renal capsule transplantation and in situ injection of alveolar socket. RESULTS: CDC42 displayed a dynamic spatiotemporal pattern, with abundant expression in HERS cells and apical DPCs in developing root. Lentivirus-mediated Cdc42 knockdown in HERS cells didn’t disrupt cell junctions as well as epithelium-mesenchyme transition. However, inhibition of CDC42 in DPCs undermined cell proliferation, migration and odontogenic differentiation. Wnt/β-catenin signaling as the downstream target of CDC42 modulated DPCs’ odontogenic differentiation. The transplantation and in situ injection experiments verified that loss of CDC42 impeded root extension via inhibiting the proliferation and differentiation of DPCs. CONCLUSIONS: We innovatively revealed that CDC42 was responsible for guiding root elongation in a mesenchyme-specific manner. Furthermore, CDC42-mediated canonical Wnt signaling regulated odontogenic differentiation of DPCs during root formation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-023-03486-2. BioMed Central 2023-09-19 /pmc/articles/PMC10510226/ /pubmed/37726858 http://dx.doi.org/10.1186/s13287-023-03486-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhou, Tao
Chen, Guoqing
Xu, Yuchan
Zhang, Shuning
Tang, Huilin
Qiu, Tao
Guo, Weihua
CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation
title CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation
title_full CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation
title_fullStr CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation
title_full_unstemmed CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation
title_short CDC42-mediated Wnt signaling facilitates odontogenic differentiation of DPCs during tooth root elongation
title_sort cdc42-mediated wnt signaling facilitates odontogenic differentiation of dpcs during tooth root elongation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510226/
https://www.ncbi.nlm.nih.gov/pubmed/37726858
http://dx.doi.org/10.1186/s13287-023-03486-2
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