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      Nucleotide receptor P2RY4 is required for head formation via induction and maintenance of head organizer in Xenopus laevis

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          Abstract

          Vertebrates have unique head structures that are mainly composed of the central nervous system, the neural crest, and placode cells. These head structures are brought about initially by the neural induction between the organizer and the prospective neuroectoderm at early gastrula stage. Purinergic receptors are activated by nucleotides released from cells and influence intracellular signaling pathways, such as phospholipase C and adenylate cyclase signaling pathways. As P2Y receptor is vertebrate‐specific and involved in head formation, we expect that its emergence may be related to the acquisition of vertebrate head during evolution. Here, we focused on the role of p2ry4 in early development in Xenopus laevis and found that p2ry4 was required for the establishment of the head organizer during neural induction and contributed to head formation. We showed that p2ry4 was expressed in the head organizer region and the prospective neuroectoderm at early gastrula stage, and was enriched in the head components. Disruption of p2ry4 function resulted in the small head phenotype and the reduced expression of marker genes specific for neuroectoderm and neural border at an early neurula stage. Furthermore, we examined the effect of p2ry4 disruption on the establishment of the head organizer and found that a reduction in the expression of head organizer genes, such as dkk1 and cerberus, and p2ry4 could also induce the ectopic expression of these marker genes. These results suggested that p2ry4 plays a key role in head organizer formation. Our study demonstrated a novel role of p2ry4 in early head development.

          Abstract

          P2Y4 receptor is required for the formation of head organizer and function in the following induction process of neural and neural crest. We demonstrated a novel role of p2ry4 in early head development.

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          Most cited references46

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          International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy.

          There have been many advances in our knowledge about different aspects of P2Y receptor signaling since the last review published by our International Union of Pharmacology subcommittee. More receptor subtypes have been cloned and characterized and most orphan receptors de-orphanized, so that it is now possible to provide a basis for a future subdivision of P2Y receptor subtypes. More is known about the functional elements of the P2Y receptor molecules and the signaling pathways involved, including interactions with ion channels. There have been substantial developments in the design of selective agonists and antagonists to some of the P2Y receptor subtypes. There are new findings about the mechanisms underlying nucleotide release and ectoenzymatic nucleotide breakdown. Interactions between P2Y receptors and receptors to other signaling molecules have been explored as well as P2Y-mediated control of gene transcription. The distribution and roles of P2Y receptor subtypes in many different cell types are better understood and P2Y receptor-related compounds are being explored for therapeutic purposes. These and other advances are discussed in the present review.
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            In situ hybridization: an improved whole-mount method for Xenopus embryos.

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              Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos.

              We have cloned a cDNA encoding a novel polypeptide capable of inducing dorsal development in Xenopus embryos. RNA transcripts from this clone rescue normal development when injected into ventralized embryos and result in excessive head development at high doses. Therefore, we have named the cDNA noggin, noggin cDNA contains a single reading frame encoding a 26 kd protein with a hydrophobic amino-terminal sequence, suggesting that it is secreted. In Northern blot analysis this cDNA hybridizes to two mRNAs that are expressed both maternally and zygotically. Although noggin transcript is not localized in the oocyte and cleavage stage embryo, zygotic transcripts are initially restricted to the presumptive dorsal mesoderm and reach their highest levels at the gastrula stage in the dorsal lip of the blastopore (Spemann organizer). In the neurula, noggin is transcribed in the notochord and prechordal mesoderm. The activity of exogenous noggin RNA in embryonic axis induction and the localized expression of endogenous noggin transcripts suggest that noggin plays a role in normal dorsal development.
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                Author and article information

                Contributors
                hashimoto@brh.co.jp
                Journal
                Dev Growth Differ
                Dev. Growth Differ
                10.1111/(ISSN)1440-169X
                DGD
                Development, Growth & Differentiation
                John Wiley and Sons Inc. (Hoboken )
                0012-1592
                1440-169X
                01 August 2018
                February 2019
                : 61
                : 2 ( doiID: 10.1111/dgd.2019.61.issue-2 )
                : 186-197
                Affiliations
                [ 1 ] JT Biohistory Research Hall Takatsuki Japan
                [ 2 ] Department of Mathematical and Life Sciences Graduate School of Science Hiroshima University Higashi‐Hiroshima Japan
                [ 3 ] Department of Biological Sciences Graduate School of Science Osaka University Toyonaka Japan
                Author notes
                [*] [* ] Correspondence

                Chikara Hashimoto, JT Biohistory Research Hall, 1‐1 Murasaki‐cho, Takatsuki, Osaka 569‐1125, Japan.

                Email: hashimoto@ 123456brh.co.jp

                Author information
                http://orcid.org/0000-0002-1240-0410
                Article
                DGD12563
                10.1111/dgd.12563
                7379700
                30069871
                01366e08-0e95-4d25-91ff-27fa00a4129d
                © 2018 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 November 2017
                : 05 July 2018
                : 08 July 2018
                Page count
                Figures: 5, Tables: 0, Pages: 12, Words: 8203
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                February 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:24.07.2020

                Developmental biology
                head formation,head organizer,p2y receptor,xenopus laevis
                Developmental biology
                head formation, head organizer, p2y receptor, xenopus laevis

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