Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation
The Hippo signaling pathway has been shown to be involved in regulating cellular identity, cell/tissue size maintenance and mechanotransduction. The Hippo pathway consists of a kinase cascade which determines the nucleo-cytoplasmic localization of YAP in the cell. YAP is the effector protein in the...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.676182/full |
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| author | Manu Unni Manu Unni Puli Chandramouli Reddy Mrinmoy Pal Irit Sagi Sanjeev Galande Sanjeev Galande |
| author_facet | Manu Unni Manu Unni Puli Chandramouli Reddy Mrinmoy Pal Irit Sagi Sanjeev Galande Sanjeev Galande |
| author_sort | Manu Unni |
| collection | DOAJ |
| description | The Hippo signaling pathway has been shown to be involved in regulating cellular identity, cell/tissue size maintenance and mechanotransduction. The Hippo pathway consists of a kinase cascade which determines the nucleo-cytoplasmic localization of YAP in the cell. YAP is the effector protein in the Hippo pathway, which acts as a transcriptional cofactor for TEAD. Phosphorylation of YAP upon activation of the Hippo pathway prevents it from entering the nucleus and abrogates its function in the transcription of the target genes. In Cnidaria, the information on the regulatory roles of the Hippo pathway is virtually lacking. Here, we report the existence of a complete set of Hippo pathway core components in Hydra for the first time. By studying their phylogeny and domain organization, we report evolutionary conservation of the components of the Hippo pathway. Protein modelling suggested the conservation of YAP-TEAD interaction in Hydra. Further, we characterized the expression pattern of the homologs of yap, hippo, mob and sav in Hydra using whole-mount RNA in situ hybridization and report their possible role in stem cell maintenance. Immunofluorescence assay revealed that Hvul_YAP expressing cells occur in clusters in the body column and are excluded in the terminally differentiated regions. Actively proliferating cells marked by Ki67 exhibit YAP colocalization in their nuclei. Strikingly, a subset of these colocalized cells is actively recruited to the newly developing bud. Disruption of the YAP-TEAD interaction increased the budding rate indicating a critical role of YAP in regulating cell proliferation in Hydra. Collectively, we posit that the Hippo pathway is an essential signaling system in Hydra; its components are ubiquitously expressed in the Hydra body column and play a crucial role in Hydra tissue homeostasis. |
| first_indexed | 2024-12-22T10:21:57Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-22T10:21:57Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-a0af310f4c8d4e5594f518bacc7fabde2022-12-21T18:29:37ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-10-011210.3389/fgene.2021.676182676182Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and DifferentiationManu Unni0Manu Unni1Puli Chandramouli Reddy2Mrinmoy Pal3Irit Sagi4Sanjeev Galande5Sanjeev Galande6Centre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research, Pune, IndiaDepartment of Biological Regulation, Weizmann Institute of Science, Rehovot, IsraelCentre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research, Pune, IndiaCentre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research, Pune, IndiaDepartment of Biological Regulation, Weizmann Institute of Science, Rehovot, IsraelCentre of Excellence in Epigenetics, Department of Biology, Indian Institute of Science Education and Research, Pune, IndiaDepartment of Life Sciences, Shiv Nadar University, Delhi-NCR, IndiaThe Hippo signaling pathway has been shown to be involved in regulating cellular identity, cell/tissue size maintenance and mechanotransduction. The Hippo pathway consists of a kinase cascade which determines the nucleo-cytoplasmic localization of YAP in the cell. YAP is the effector protein in the Hippo pathway, which acts as a transcriptional cofactor for TEAD. Phosphorylation of YAP upon activation of the Hippo pathway prevents it from entering the nucleus and abrogates its function in the transcription of the target genes. In Cnidaria, the information on the regulatory roles of the Hippo pathway is virtually lacking. Here, we report the existence of a complete set of Hippo pathway core components in Hydra for the first time. By studying their phylogeny and domain organization, we report evolutionary conservation of the components of the Hippo pathway. Protein modelling suggested the conservation of YAP-TEAD interaction in Hydra. Further, we characterized the expression pattern of the homologs of yap, hippo, mob and sav in Hydra using whole-mount RNA in situ hybridization and report their possible role in stem cell maintenance. Immunofluorescence assay revealed that Hvul_YAP expressing cells occur in clusters in the body column and are excluded in the terminally differentiated regions. Actively proliferating cells marked by Ki67 exhibit YAP colocalization in their nuclei. Strikingly, a subset of these colocalized cells is actively recruited to the newly developing bud. Disruption of the YAP-TEAD interaction increased the budding rate indicating a critical role of YAP in regulating cell proliferation in Hydra. Collectively, we posit that the Hippo pathway is an essential signaling system in Hydra; its components are ubiquitously expressed in the Hydra body column and play a crucial role in Hydra tissue homeostasis.https://www.frontiersin.org/articles/10.3389/fgene.2021.676182/fullhydrahippo pathwayYAPbuddingcell prolferation |
| spellingShingle | Manu Unni Manu Unni Puli Chandramouli Reddy Mrinmoy Pal Irit Sagi Sanjeev Galande Sanjeev Galande Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation Frontiers in Genetics hydra hippo pathway YAP budding cell prolferation |
| title | Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation |
| title_full | Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation |
| title_fullStr | Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation |
| title_full_unstemmed | Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation |
| title_short | Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation |
| title_sort | identification of components of the hippo pathway in hydra and potential role of yap in cell division and differentiation |
| topic | hydra hippo pathway YAP budding cell prolferation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.676182/full |
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