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      Hippo signalling during development

      research-article
      Author(s): , *
      Publication date (Electronic):
      Journal: Development (Cambridge, England)
      Keywords: Cell fate, Differentiation, Growth, Hippo pathway, Morphogenesis, YAP

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          Abstract

          The Hippo signalling pathway and its transcriptional co-activator targets Yorkie/YAP/TAZ first came to attention because of their role in tissue growth control. Over the past 15 years, it has become clear that, like other developmental pathways (e.g. the Wnt, Hedgehog and TGFβ pathways), Hippo signalling is a ‘jack of all trades’ that is reiteratively used to mediate a range of cellular decision-making processes from proliferation, death and morphogenesis to cell fate determination. Here, and in the accompanying poster, we briefly outline the core pathway and its regulation, and describe the breadth of its roles in animal development.

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          Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling.

          Fa-Xing Yu, Bin Zhao, Nattapon Panupinthu … (2012)
          The Hippo pathway is crucial in organ size control, and its dysregulation contributes to tumorigenesis. However, upstream signals that regulate the mammalian Hippo pathway have remained elusive. Here, we report that the Hippo pathway is regulated by G-protein-coupled receptor (GPCR) signaling. Serum-borne lysophosphatidic acid (LPA) and sphingosine 1-phosphophate (S1P) act through G12/13-coupled receptors to inhibit the Hippo pathway kinases Lats1/2, thereby activating YAP and TAZ transcription coactivators, which are oncoproteins repressed by Lats1/2. YAP and TAZ are involved in LPA-induced gene expression, cell migration, and proliferation. In contrast, stimulation of Gs-coupled receptors by glucagon or epinephrine activates Lats1/2 kinase activity, thereby inhibiting YAP function. Thus, GPCR signaling can either activate or inhibit the Hippo-YAP pathway depending on the coupled G protein. Our study identifies extracellular diffusible signals that modulate the Hippo pathway and also establishes the Hippo-YAP pathway as a critical signaling branch downstream of GPCR. Copyright © 2012 Elsevier Inc. All rights reserved.
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            The extracellular matrix protein agrin promotes heart regeneration in mice

            Elad Bassat, Yara Mutlak, Alex Genzelinakh … (2017)
            The adult mammalian heart is non-regenerative owing to the post-mitotic nature of cardiomyocytes. The neonatal mouse heart can regenerate, but only during the first week of life. Here we show that changes in the composition of the extracellular matrix during this week can affect cardiomyocyte
            Article 0 comments Cited 274 times – based on 0 reviews     Review now
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              The Hippo signaling pathway in stem cell biology and cancer.

              Jung-Soon Mo, Hyun Park, Kun-Liang Guan (2014)
              The Hippo signaling pathway, consisting of a highly conserved kinase cascade (MST and Lats) and downstream transcription coactivators (YAP and TAZ), plays a key role in tissue homeostasis and organ size control by regulating tissue-specific stem cells. Moreover, this pathway plays a prominent role in tissue repair and regeneration. Dysregulation of the Hippo pathway is associated with cancer development. Recent studies have revealed a complex network of upstream inputs, including cell density, mechanical sensation, and G-protein-coupled receptor (GPCR) signaling, that modulate Hippo pathway activity. This review focuses on the role of the Hippo pathway in stem cell biology and its potential implications in tissue homeostasis and cancer.
              Article 0 comments Cited 274 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 8701744
                Journal ID (nlm-ta): Development
                Journal ID (iso-abbrev): Development
                Title: Development (Cambridge, England)
                ISSN (Print): 0950-1991
                ISSN (Electronic): 1477-9129
                Publication date (Print): 16 September 2019
                Publication date (Electronic): 16 September 2019
                Publication date Nihms-submitted: 02 March 2020
                Publication date PMC-release: 27 March 2020
                Volume: 146
                Issue: 18
                Electronic Location Identifier: dev167106
                Affiliations
                Apoptosis and Proliferation Control Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
                Author notes
                [* ]Author for correspondence ( nic.tapon@ 123456crick.ac.uk )
                Article
                Manuscript ID: EMS85948
                DOI: 10.1242/dev.167106
                PMC ID: 7100553
                PubMed ID: 31527062
                SO-VID: 2019c76b-ca73-4c5a-ba7b-0b58d91a35c8
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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                Subject: Article

                ScienceOpen disciplines: Developmental biology
                Keywords: cell fate,differentiation,growth,hippo pathway,morphogenesis,yap
                Data availability:
                ScienceOpen disciplines: Developmental biology
                Keywords: cell fate, differentiation, growth, hippo pathway, morphogenesis, yap

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