{"scopus_import":"1","acknowledgement":"We thank the members of the Matsuda Laboratory for their helpful discussion and encouragement, and we thank K. Hirano and K. Takakura for their technical assistance. This work was supported by the Kyoto University Live Imaging Center. Financial support was provided in the form of JSPS KAKENHI grants (nos. 17J02107 and 20K22653 to N.H., and 20H05898 and 19H00993 to M.M.), a JST CREST grant (no. JPMJCR1654 to M.M.), a Moonshot R&D grant (no. JPMJPS2022-11 to M.M.), Generalitat de Catalunya and the CERCA Programme (no. SGR-2017-01602 to X.T.), MICCINN/FEDER (no. PGC2018-099645-B-I00 to X.T.), and European Research Council (no. Adv-883739 to X.T.). IBEC is a recipient of a Severo Ochoa Award of Excellence from the MINECO. This work was partly supported by an Extramural Collaborative Research Grant of Cancer Research Institute, Kanazawa University.","intvolume":" 57","volume":57,"day":"01","oa_version":"None","publisher":"Elsevier","date_updated":"2023-08-04T09:38:53Z","month":"10","publication_status":"published","page":"2290-2304.e7","date_published":"2022-10-01T00:00:00Z","abstract":[{"lang":"eng","text":"Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Förster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration."}],"article_processing_charge":"No","isi":1,"status":"public","department":[{"_id":"CaHe"}],"author":[{"first_name":"Naoya","last_name":"Hino","id":"5299a9ce-7679-11eb-a7bc-d1e62b936307","full_name":"Hino, Naoya"},{"last_name":"Matsuda","full_name":"Matsuda, Kimiya","first_name":"Kimiya"},{"first_name":"Yuya","last_name":"Jikko","full_name":"Jikko, Yuya"},{"full_name":"Maryu, Gembu","last_name":"Maryu","first_name":"Gembu"},{"full_name":"Sakai, Katsuya","last_name":"Sakai","first_name":"Katsuya"},{"last_name":"Imamura","full_name":"Imamura, Ryu","first_name":"Ryu"},{"first_name":"Shinya","full_name":"Tsukiji, Shinya","last_name":"Tsukiji"},{"full_name":"Aoki, Kazuhiro","last_name":"Aoki","first_name":"Kazuhiro"},{"first_name":"Kenta","last_name":"Terai","full_name":"Terai, Kenta"},{"first_name":"Tsuyoshi","last_name":"Hirashima","full_name":"Hirashima, Tsuyoshi"},{"first_name":"Xavier","last_name":"Trepat","full_name":"Trepat, Xavier"},{"last_name":"Matsuda","full_name":"Matsuda, Michiyuki","first_name":"Michiyuki"}],"citation":{"mla":"Hino, Naoya, et al. “A Feedback Loop between Lamellipodial Extension and HGF-ERK Signaling Specifies Leader Cells during Collective Cell Migration.” Developmental Cell, vol. 57, no. 19, Elsevier, 2022, p. 2290–2304.e7, doi:10.1016/j.devcel.2022.09.003.","ama":"Hino N, Matsuda K, Jikko Y, et al. A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration. Developmental Cell. 2022;57(19):2290-2304.e7. doi:10.1016/j.devcel.2022.09.003","ieee":"N. Hino et al., “A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration,” Developmental Cell, vol. 57, no. 19. Elsevier, p. 2290–2304.e7, 2022.","short":"N. Hino, K. Matsuda, Y. Jikko, G. Maryu, K. Sakai, R. Imamura, S. Tsukiji, K. Aoki, K. Terai, T. Hirashima, X. Trepat, M. Matsuda, Developmental Cell 57 (2022) 2290–2304.e7.","apa":"Hino, N., Matsuda, K., Jikko, Y., Maryu, G., Sakai, K., Imamura, R., … Matsuda, M. (2022). A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2022.09.003","ista":"Hino N, Matsuda K, Jikko Y, Maryu G, Sakai K, Imamura R, Tsukiji S, Aoki K, Terai K, Hirashima T, Trepat X, Matsuda M. 2022. A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration. Developmental Cell. 57(19), 2290–2304.e7.","chicago":"Hino, Naoya, Kimiya Matsuda, Yuya Jikko, Gembu Maryu, Katsuya Sakai, Ryu Imamura, Shinya Tsukiji, et al. “A Feedback Loop between Lamellipodial Extension and HGF-ERK Signaling Specifies Leader Cells during Collective Cell Migration.” Developmental Cell. Elsevier, 2022. https://doi.org/10.1016/j.devcel.2022.09.003."},"type":"journal_article","year":"2022","date_created":"2023-01-16T09:51:39Z","publication":"Developmental Cell","doi":"10.1016/j.devcel.2022.09.003","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"pmid":["36174555"],"isi":["000898428700006"]},"quality_controlled":"1","title":"A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration","issue":"19","article_type":"original","keyword":["Developmental Biology","Cell Biology","General Biochemistry","Genetics and Molecular Biology","Molecular Biology"],"publication_identifier":{"issn":["1534-5807"]},"language":[{"iso":"eng"}],"pmid":1,"_id":"12238"}