{"department":[{"_id":"EdHa"}],"abstract":[{"text":"The sculpting of germ layers during gastrulation relies on the coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor–based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.","lang":"eng"}],"date_published":"2022-09-14T00:00:00Z","publication_status":"published","issue":"37","article_processing_charge":"No","month":"09","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"pmid":1,"date_updated":"2023-08-04T09:49:59Z","file":[{"date_updated":"2023-01-30T09:27:49Z","date_created":"2023-01-30T09:27:49Z","file_size":1636732,"file_id":"12444","success":1,"relation":"main_file","checksum":"f59cdb824e5d4221045def81f46f6c65","file_name":"2022_ScienceAdvances_Stock.pdf","creator":"dernst","access_level":"open_access","content_type":"application/pdf"}],"type":"journal_article","day":"14","quality_controlled":"1","title":"A self-generated Toddler gradient guides mesodermal cell migration","status":"public","publisher":"American Association for the Advancement of Science","scopus_import":"1","oa":1,"oa_version":"Published Version","date_created":"2023-01-16T09:57:10Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","language":[{"iso":"eng"}],"article_number":"eadd2488","_id":"12253","ec_funded":1,"article_type":"original","citation":{"ieee":"J. Stock, T. Kazmar, F. Schlumm, E. B. Hannezo, and A. Pauli, “A self-generated Toddler gradient guides mesodermal cell migration,” <i>Science Advances</i>, vol. 8, no. 37. American Association for the Advancement of Science, 2022.","mla":"Stock, Jessica, et al. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” <i>Science Advances</i>, vol. 8, no. 37, eadd2488, American Association for the Advancement of Science, 2022, doi:<a href=\"https://doi.org/10.1126/sciadv.add2488\">10.1126/sciadv.add2488</a>.","short":"J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances 8 (2022).","ista":"Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. 2022. A self-generated Toddler gradient guides mesodermal cell migration. Science Advances. 8(37), eadd2488.","chicago":"Stock, Jessica, Tomas Kazmar, Friederike Schlumm, Edouard B Hannezo, and Andrea Pauli. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” <i>Science Advances</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/sciadv.add2488\">https://doi.org/10.1126/sciadv.add2488</a>.","apa":"Stock, J., Kazmar, T., Schlumm, F., Hannezo, E. B., &#38; Pauli, A. (2022). A self-generated Toddler gradient guides mesodermal cell migration. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.add2488\">https://doi.org/10.1126/sciadv.add2488</a>","ama":"Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. A self-generated Toddler gradient guides mesodermal cell migration. <i>Science Advances</i>. 2022;8(37). doi:<a href=\"https://doi.org/10.1126/sciadv.add2488\">10.1126/sciadv.add2488</a>"},"external_id":{"isi":["000888875000009"],"pmid":["36103529"]},"publication_identifier":{"issn":["2375-2548"]},"doi":"10.1126/sciadv.add2488","author":[{"full_name":"Stock, Jessica","last_name":"Stock","first_name":"Jessica"},{"last_name":"Kazmar","first_name":"Tomas","full_name":"Kazmar, Tomas"},{"last_name":"Schlumm","first_name":"Friederike","full_name":"Schlumm, Friederike"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"first_name":"Andrea","last_name":"Pauli","full_name":"Pauli, Andrea"}],"has_accepted_license":"1","publication":"Science Advances","ddc":["570"],"project":[{"call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288"}],"file_date_updated":"2023-01-30T09:27:49Z","acknowledgement":"We thank K. Aumayer and the team of the biooptics facility at the Vienna Biocenter, particularly P. Pasierbek and T. Müller, for support with microscopy; K. Panser, C. Pribitzer, and the animal facility personnel for taking care of zebrafish; M. Binner and A. Bandura for help with genotyping; M. Codina Tobias for help with establishing the conditions for the Toddler overexpression compensation experiment; T. Lubiana Alves for sharing the code for scRNA-Seq analyses; the Heisenberg laboratory, particularly D. Pinheiro, for joint laboratory meetings, discussions on the project, and providing the tg(gsc:CAAX-GFP) fish line; the Raz laboratory for providing the Lifeact-GFP plasmid; A. Andersen, A. Schier, C.-P. Heisenberg, and E. Tanaka for comments on the manuscript; and the entire Pauli laboratory, particularly K. Gert and V. Deneke, for valuable discussions and feedback on the manuscript. Funding: Work in A.P.’s laboratory has been supported by the IMP, which receives institutional funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter grant FFG-852936), as well as the FWF START program (Y 1031-B28 to A.P.), the Human Frontier Science Program (HFSP) Career Development Award (CDA00066/2015 to A.P.) and Young Investigator Grant (RGY0079/2020 to A.P.), the SFB RNA-Deco (project number F 80 to A.P.), a Whitman Center Fellowship from the Marine Biological Laboratory (to A.P.), and EMBO-YIP funds (to A.P.). This work was supported by the European Union (European Research Council Starting Grant 851288 to E.H.). For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript (AAM) version arising from this submission.","isi":1,"year":"2022","intvolume":"         8","volume":8}