Cargando…
CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport
Ciliated and secretory cells are two major cell types that comprise the oviduct epithelia. Accumulating evidences support a role of oviductal multiciliated epithelia for embryo transport, however the mechanisms underlying this specialized cell type differentiation remain elusive. Here, we report tha...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440026/ https://www.ncbi.nlm.nih.gov/pubmed/36056002 http://dx.doi.org/10.1038/s41419-022-05184-y |
_version_ | 1784782220029853696 |
---|---|
author | Jiang, Ruiwei Tang, Xiaofang Pan, Jiale Li, Gaizhen Yang, Ningjie Tang, Yedong Bi, Shilei Cai, Han Chen, Qionghua Chen, Dunjin Wang, Haibin Kong, Shuangbo |
author_facet | Jiang, Ruiwei Tang, Xiaofang Pan, Jiale Li, Gaizhen Yang, Ningjie Tang, Yedong Bi, Shilei Cai, Han Chen, Qionghua Chen, Dunjin Wang, Haibin Kong, Shuangbo |
author_sort | Jiang, Ruiwei |
collection | PubMed |
description | Ciliated and secretory cells are two major cell types that comprise the oviduct epithelia. Accumulating evidences support a role of oviductal multiciliated epithelia for embryo transport, however the mechanisms underlying this specialized cell type differentiation remain elusive. Here, we report that CDC42 depletion in oviduct epithelia hampers the morphogenesis of multiciliated cell, and results in embryo retention, leading to early pregnancy failure. Utilizing the oviduct organoid model, we further observed that CDC42 guides secretory cells transition into multiciliated cells independent of its GTPase activity and the well-known Notch pathway. Further exploration uncovered the AKT as a novel indispensable regulator for multiciliated cells differentiation, whose activity was maintained by CDC42 through interacting with the p110β. Consistently, re-activating AKT partially incites multiciliated cells differentiation in Cdc42 knockout oviductal organoids. Finally, low levels of CDC42 and phospho-AKT with reduced multiciliated cells in the oviduct are observed in women with ectopic pregnancy. Collectively, we provide previously unappreciated evidence that CDC42-AKT signaling is a critical determinant for morphogenesis of oviduct multiciliated cell, which possesses the clinical application in understanding the pathology of ectopic pregnancy and facilitating the development of prevention strategies. |
format | Online Article Text |
id | pubmed-9440026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94400262022-09-04 CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport Jiang, Ruiwei Tang, Xiaofang Pan, Jiale Li, Gaizhen Yang, Ningjie Tang, Yedong Bi, Shilei Cai, Han Chen, Qionghua Chen, Dunjin Wang, Haibin Kong, Shuangbo Cell Death Dis Article Ciliated and secretory cells are two major cell types that comprise the oviduct epithelia. Accumulating evidences support a role of oviductal multiciliated epithelia for embryo transport, however the mechanisms underlying this specialized cell type differentiation remain elusive. Here, we report that CDC42 depletion in oviduct epithelia hampers the morphogenesis of multiciliated cell, and results in embryo retention, leading to early pregnancy failure. Utilizing the oviduct organoid model, we further observed that CDC42 guides secretory cells transition into multiciliated cells independent of its GTPase activity and the well-known Notch pathway. Further exploration uncovered the AKT as a novel indispensable regulator for multiciliated cells differentiation, whose activity was maintained by CDC42 through interacting with the p110β. Consistently, re-activating AKT partially incites multiciliated cells differentiation in Cdc42 knockout oviductal organoids. Finally, low levels of CDC42 and phospho-AKT with reduced multiciliated cells in the oviduct are observed in women with ectopic pregnancy. Collectively, we provide previously unappreciated evidence that CDC42-AKT signaling is a critical determinant for morphogenesis of oviduct multiciliated cell, which possesses the clinical application in understanding the pathology of ectopic pregnancy and facilitating the development of prevention strategies. Nature Publishing Group UK 2022-09-02 /pmc/articles/PMC9440026/ /pubmed/36056002 http://dx.doi.org/10.1038/s41419-022-05184-y Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Jiang, Ruiwei Tang, Xiaofang Pan, Jiale Li, Gaizhen Yang, Ningjie Tang, Yedong Bi, Shilei Cai, Han Chen, Qionghua Chen, Dunjin Wang, Haibin Kong, Shuangbo CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport |
title | CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport |
title_full | CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport |
title_fullStr | CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport |
title_full_unstemmed | CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport |
title_short | CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport |
title_sort | cdc42 governs normal oviduct multiciliogenesis through activating akt to ensure timely embryo transport |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440026/ https://www.ncbi.nlm.nih.gov/pubmed/36056002 http://dx.doi.org/10.1038/s41419-022-05184-y |
work_keys_str_mv | AT jiangruiwei cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT tangxiaofang cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT panjiale cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT ligaizhen cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT yangningjie cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT tangyedong cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT bishilei cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT caihan cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT chenqionghua cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT chendunjin cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT wanghaibin cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport AT kongshuangbo cdc42governsnormaloviductmulticiliogenesisthroughactivatingakttoensuretimelyembryotransport |