[{"volume":43,"extern":"1","ddc":["570"],"doi":"10.1002/humu.24435","day":"01","abstract":[{"text":"Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for faithful assignment of amino acids to their cognate tRNA. Variants in ARS genes are frequently associated with clinically heterogeneous phenotypes in humans and follow both autosomal dominant or recessive inheritance patterns in many instances. Variants in tryptophanyl-tRNA synthetase 1 (WARS1) cause autosomal dominantly inherited distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. Presently, only one family with biallelic WARS1 variants has been described. We present three affected individuals from two families with biallelic variants (p.Met1? and p.(Asp419Asn)) in WARS1, showing varying severities of developmental delay and intellectual disability. Hearing impairment and microcephaly, as well as abnormalities of the brain, skeletal system, movement/gait, and behavior were variable features. Phenotyping of knocked down wars-1 in a Caenorhabditis elegans model showed depletion is associated with defects in germ cell development. A wars1 knockout vertebrate model recapitulates the human clinical phenotypes, confirms variant pathogenicity, and uncovers evidence implicating the p.Met1? variant as potentially impacting an exon critical for normal hearing. Together, our findings provide consolidating evidence for biallelic disruption of WARS1 as causal for an autosomal recessive neurodevelopmental syndrome and present a vertebrate model that recapitulates key phenotypes observed in patients.","lang":"eng"}],"date_updated":"2023-09-25T08:54:14Z","year":"2022","citation":{"ista":"Lin S-J, Vona B, Porter HM, Izadi M, Huang K, Lacassie Y, Rosenfeld JA, Khan S, Petree C, Ali TA, Muhammad N, Khan SA, Muhammad N, Liu P, Haymon M-L, Rueschendorf F, Kong I-K, Schnapp L, Shur N, Chorich L, Layman L, Haaf T, Pourkarimi E, Kim H-G, Varshney GK. 2022. Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function. Human Mutation. 43(10), 1472–1489.","mla":"Lin, Sheng-Jia, et al. “Biallelic Variants in WARS1 Cause a Highly Variable Neurodevelopmental Syndrome and Implicate a Critical Exon for Normal Auditory Function.” <i>Human Mutation</i>, vol. 43, no. 10, Wiley, 2022, pp. 1472–89, doi:<a href=\"https://doi.org/10.1002/humu.24435\">10.1002/humu.24435</a>.","short":"S.-J. Lin, B. Vona, H.M. Porter, M. Izadi, K. Huang, Y. Lacassie, J.A. Rosenfeld, S. Khan, C. Petree, T.A. Ali, N. Muhammad, S.A. Khan, N. Muhammad, P. Liu, M.-L. Haymon, F. Rueschendorf, I.-K. Kong, L. Schnapp, N. Shur, L. Chorich, L. Layman, T. Haaf, E. Pourkarimi, H.-G. Kim, G.K. Varshney, Human Mutation 43 (2022) 1472–1489.","chicago":"Lin, Sheng-Jia, Barbara Vona, Hillary M. Porter, Mahmoud Izadi, Kevin Huang, Yves Lacassie, Jill A. Rosenfeld, et al. “Biallelic Variants in WARS1 Cause a Highly Variable Neurodevelopmental Syndrome and Implicate a Critical Exon for Normal Auditory Function.” <i>Human Mutation</i>. Wiley, 2022. <a href=\"https://doi.org/10.1002/humu.24435\">https://doi.org/10.1002/humu.24435</a>.","ieee":"S.-J. Lin <i>et al.</i>, “Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function,” <i>Human Mutation</i>, vol. 43, no. 10. Wiley, pp. 1472–1489, 2022.","apa":"Lin, S.-J., Vona, B., Porter, H. M., Izadi, M., Huang, K., Lacassie, Y., … Varshney, G. K. (2022). Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function. <i>Human Mutation</i>. Wiley. <a href=\"https://doi.org/10.1002/humu.24435\">https://doi.org/10.1002/humu.24435</a>","ama":"Lin S-J, Vona B, Porter HM, et al. Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function. <i>Human Mutation</i>. 2022;43(10):1472-1489. doi:<a href=\"https://doi.org/10.1002/humu.24435\">10.1002/humu.24435</a>"},"publisher":"Wiley","article_type":"original","page":"1472-1489","quality_controlled":"1","file_date_updated":"2023-09-25T08:52:54Z","publication_status":"published","date_created":"2023-09-20T20:58:24Z","article_processing_charge":"No","title":"Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function","intvolume":"        43","_id":"14356","scopus_import":"1","author":[{"last_name":"Lin","first_name":"Sheng-Jia","full_name":"Lin, Sheng-Jia"},{"last_name":"Vona","first_name":"Barbara","full_name":"Vona, Barbara"},{"full_name":"Porter, Hillary M.","last_name":"Porter","first_name":"Hillary M."},{"full_name":"Izadi, Mahmoud","last_name":"Izadi","first_name":"Mahmoud"},{"first_name":"Kevin","last_name":"Huang","orcid":"0000-0002-2512-7812","full_name":"Huang, Kevin","id":"3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3"},{"last_name":"Lacassie","first_name":"Yves","full_name":"Lacassie, Yves"},{"last_name":"Rosenfeld","first_name":"Jill A.","full_name":"Rosenfeld, Jill A."},{"full_name":"Khan, Saadullah","first_name":"Saadullah","last_name":"Khan"},{"first_name":"Cassidy","last_name":"Petree","full_name":"Petree, Cassidy"},{"last_name":"Ali","first_name":"Tayyiba A.","full_name":"Ali, Tayyiba A."},{"full_name":"Muhammad, Nazif","last_name":"Muhammad","first_name":"Nazif"},{"full_name":"Khan, Sher A.","last_name":"Khan","first_name":"Sher A."},{"full_name":"Muhammad, Noor","first_name":"Noor","last_name":"Muhammad"},{"first_name":"Pengfei","last_name":"Liu","full_name":"Liu, Pengfei"},{"full_name":"Haymon, Marie-Louise","first_name":"Marie-Louise","last_name":"Haymon"},{"last_name":"Rueschendorf","first_name":"Franz","full_name":"Rueschendorf, Franz"},{"last_name":"Kong","first_name":"Il-Keun","full_name":"Kong, Il-Keun"},{"full_name":"Schnapp, Linda","last_name":"Schnapp","first_name":"Linda"},{"first_name":"Natasha","last_name":"Shur","full_name":"Shur, Natasha"},{"last_name":"Chorich","first_name":"Lynn","full_name":"Chorich, Lynn"},{"full_name":"Layman, Lawrence","last_name":"Layman","first_name":"Lawrence"},{"first_name":"Thomas","last_name":"Haaf","full_name":"Haaf, Thomas"},{"last_name":"Pourkarimi","first_name":"Ehsan","full_name":"Pourkarimi, Ehsan"},{"full_name":"Kim, Hyung-Goo","last_name":"Kim","first_name":"Hyung-Goo"},{"full_name":"Varshney, Gaurav K.","last_name":"Varshney","first_name":"Gaurav K."}],"issue":"10","file":[{"file_id":"14370","creator":"dernst","success":1,"relation":"main_file","access_level":"open_access","date_updated":"2023-09-25T08:52:54Z","file_name":"2022_HumanMutation_Lin.pdf","content_type":"application/pdf","date_created":"2023-09-25T08:52:54Z","checksum":"74b01d4e4084b2f64c30ed32b18ee928","file_size":12131312}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","publication_identifier":{"issn":["1059-7794"]},"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2022-10-01T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"keyword":["autosomal recessive","biallelic variants","C","elegans","translation initiation sites","tryptophanyl-tRNA synthetase 1 (WARS1)","WHEP domain","zebrafish"],"oa_version":"Published Version","month":"10","publication":"Human Mutation","has_accepted_license":"1"},{"extern":"1","ddc":["570"],"volume":43,"external_id":{"pmid":["35790048"]},"date_updated":"2023-09-25T08:43:06Z","year":"2022","citation":{"ista":"Boegershausen N, Krawczyk HE, Jamra RA, Lin S-J, Yigit G, Huening I, Polo AM, Vona B, Huang K, Schmidt J, Altmueller J, Luppe J, Platzer K, Doergeloh BB, Busche A, Biskup S, Mendes, I M, Smith DEC, Salomons GS, Zibat A, Bueltmann E, Nuernberg P, Spielmann M, Lemke JR, Li Y, Zenker M, Varshney GK, Hillen HS, Kratz CP, Wollnik B. 2022. WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly. Human Mutation. 43(10), 1454–1471.","short":"N. Boegershausen, H.E. Krawczyk, R.A. Jamra, S.-J. Lin, G. Yigit, I. Huening, A.M. Polo, B. Vona, K. Huang, J. Schmidt, J. Altmueller, J. Luppe, K. Platzer, B.B. Doergeloh, A. Busche, S. Biskup, M. Mendes, I, D.E.C. Smith, G.S. Salomons, A. Zibat, E. Bueltmann, P. Nuernberg, M. Spielmann, J.R. Lemke, Y. Li, M. Zenker, G.K. Varshney, H.S. Hillen, C.P. Kratz, B. Wollnik, Human Mutation 43 (2022) 1454–1471.","mla":"Boegershausen, Nina, et al. “WARS1 and SARS1: Two TRNA Synthetases Implicated in Autosomal Recessive Microcephaly.” <i>Human Mutation</i>, vol. 43, no. 10, Wiley, 2022, pp. 1454–71, doi:<a href=\"https://doi.org/10.1002/humu.24430\">10.1002/humu.24430</a>.","chicago":"Boegershausen, Nina, Hannah E. Krawczyk, Rami A. Jamra, Sheng-Jia Lin, Goekhan Yigit, Irina Huening, Anna M. Polo, et al. “WARS1 and SARS1: Two TRNA Synthetases Implicated in Autosomal Recessive Microcephaly.” <i>Human Mutation</i>. Wiley, 2022. <a href=\"https://doi.org/10.1002/humu.24430\">https://doi.org/10.1002/humu.24430</a>.","ieee":"N. Boegershausen <i>et al.</i>, “WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly,” <i>Human Mutation</i>, vol. 43, no. 10. Wiley, pp. 1454–1471, 2022.","apa":"Boegershausen, N., Krawczyk, H. E., Jamra, R. A., Lin, S.-J., Yigit, G., Huening, I., … Wollnik, B. (2022). WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly. <i>Human Mutation</i>. Wiley. <a href=\"https://doi.org/10.1002/humu.24430\">https://doi.org/10.1002/humu.24430</a>","ama":"Boegershausen N, Krawczyk HE, Jamra RA, et al. WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly. <i>Human Mutation</i>. 2022;43(10):1454-1471. doi:<a href=\"https://doi.org/10.1002/humu.24430\">10.1002/humu.24430</a>"},"abstract":[{"lang":"eng","text":"Aminoacylation of transfer RNA (tRNA) is a key step in protein biosynthesis, carried out by highly specific aminoacyl-tRNA synthetases (ARSs). ARSs have been implicated in autosomal dominant and autosomal recessive human disorders. Autosomal dominant variants in tryptophanyl-tRNA synthetase 1 (WARS1) are known to cause distal hereditary motor neuropathy and Charcot-Marie-Tooth disease, but a recessively inherited phenotype is yet to be clearly defined. Seryl-tRNA synthetase 1 (SARS1) has rarely been implicated in an autosomal recessive developmental disorder. Here, we report five individuals with biallelic missense variants in WARS1 or SARS1, who presented with an overlapping phenotype of microcephaly, developmental delay, intellectual disability, and brain anomalies. Structural mapping showed that the SARS1 variant is located directly within the enzyme’s active site, most likely diminishing activity, while the WARS1 variant is located in the N-terminal domain. We further characterize the identified WARS1 variant by showing that it negatively impacts protein abundance and is unable to rescue the phenotype of a CRISPR/Cas9 wars1 knockout zebrafish model. In summary, we describe two overlapping autosomal recessive syndromes caused by variants in WARS1 and SARS1, present functional insights into the pathogenesis of the WARS1-related syndrome and define an emerging disease spectrum: ARS-related developmental disorders with or without microcephaly."}],"doi":"10.1002/humu.24430","day":"01","file_date_updated":"2023-09-25T08:41:23Z","page":"1454-1471","quality_controlled":"1","article_type":"original","publisher":"Wiley","author":[{"last_name":"Boegershausen","first_name":"Nina","full_name":"Boegershausen, Nina"},{"full_name":"Krawczyk, Hannah E.","last_name":"Krawczyk","first_name":"Hannah E."},{"full_name":"Jamra, Rami A.","last_name":"Jamra","first_name":"Rami A."},{"first_name":"Sheng-Jia","last_name":"Lin","full_name":"Lin, Sheng-Jia"},{"first_name":"Goekhan","last_name":"Yigit","full_name":"Yigit, Goekhan"},{"full_name":"Huening, Irina","last_name":"Huening","first_name":"Irina"},{"first_name":"Anna M.","last_name":"Polo","full_name":"Polo, Anna M."},{"full_name":"Vona, Barbara","first_name":"Barbara","last_name":"Vona"},{"orcid":"0000-0002-2512-7812","full_name":"Huang, Kevin","first_name":"Kevin","last_name":"Huang","id":"3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3"},{"last_name":"Schmidt","first_name":"Julia","full_name":"Schmidt, Julia"},{"last_name":"Altmueller","first_name":"Janine","full_name":"Altmueller, Janine"},{"full_name":"Luppe, Johannes","last_name":"Luppe","first_name":"Johannes"},{"full_name":"Platzer, Konrad","first_name":"Konrad","last_name":"Platzer"},{"first_name":"Beate B.","last_name":"Doergeloh","full_name":"Doergeloh, Beate B."},{"first_name":"Andreas","last_name":"Busche","full_name":"Busche, Andreas"},{"first_name":"Saskia","last_name":"Biskup","full_name":"Biskup, Saskia"},{"full_name":"Mendes, I, Marisa","last_name":"Mendes, I","first_name":"Marisa"},{"full_name":"Smith, Desiree E. C.","last_name":"Smith","first_name":"Desiree E. C."},{"last_name":"Salomons","first_name":"Gajja S.","full_name":"Salomons, Gajja S."},{"first_name":"Arne","last_name":"Zibat","full_name":"Zibat, Arne"},{"first_name":"Eva","last_name":"Bueltmann","full_name":"Bueltmann, Eva"},{"full_name":"Nuernberg, Peter","first_name":"Peter","last_name":"Nuernberg"},{"first_name":"Malte","last_name":"Spielmann","full_name":"Spielmann, Malte"},{"first_name":"Johannes R.","last_name":"Lemke","full_name":"Lemke, Johannes R."},{"first_name":"Yun","last_name":"Li","full_name":"Li, Yun"},{"last_name":"Zenker","first_name":"Martin","full_name":"Zenker, Martin"},{"full_name":"Varshney, Gaurav K.","first_name":"Gaurav K.","last_name":"Varshney"},{"first_name":"Hauke S.","last_name":"Hillen","full_name":"Hillen, Hauke S."},{"last_name":"Kratz","first_name":"Christian P.","full_name":"Kratz, Christian P."},{"last_name":"Wollnik","first_name":"Bernd","full_name":"Wollnik, Bernd"}],"issue":"10","_id":"14357","pmid":1,"scopus_import":"1","title":"WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly","intvolume":"        43","publication_status":"published","article_processing_charge":"No","date_created":"2023-09-20T20:59:33Z","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_updated":"2023-09-25T08:41:23Z","content_type":"application/pdf","file_name":"2022_HumanMutation_Boegershausen.pdf","date_created":"2023-09-25T08:41:23Z","file_size":4863605,"checksum":"c31fc91e0445c35b9da83eb911a9b552","file_id":"14367","creator":"dernst","success":1,"relation":"main_file","access_level":"open_access"}],"date_published":"2022-10-01T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"publication_identifier":{"issn":["1059-7794"]},"language":[{"iso":"eng"}],"keyword":["aminoacylation","aminoacyl-tRNA synthetase","ARS","CRISPR","Cas9","intellectual disability","microcephaly","SARS1","tRNA","WARS1","zebrafish"],"publication":"Human Mutation","has_accepted_license":"1","month":"10","oa_version":"Published Version"},{"keyword":["Tissue tension","Morphogenesis","Laser ablation","Zebrafish folliculogenesis","Granulosa cells"],"language":[{"iso":"eng"}],"publication":"Germline Development in the Zebrafish","month":"02","project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"oa_version":"None","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","type":"book_chapter","date_published":"2021-02-20T00:00:00Z","publication_identifier":{"eisbn":["978-1-0716-0970-5"],"issn":["1064-3745"],"eissn":["1940-6029"],"isbn":["978-1-0716-0969-9"]},"quality_controlled":"1","ec_funded":1,"page":"117-128","editor":[{"last_name":"Dosch","first_name":"Roland","full_name":"Dosch, Roland"}],"publisher":"Humana","author":[{"id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5419-7756","full_name":"Xia, Peng","first_name":"Peng","last_name":"Xia"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","_id":"9245","pmid":1,"intvolume":"      2218","title":"Quantifying tissue tension in the granulosa layer after laser surgery","alternative_title":["Methods in Molecular Biology"],"department":[{"_id":"CaHe"}],"date_created":"2021-03-14T23:01:34Z","article_processing_charge":"No","publication_status":"published","volume":2218,"acknowledgement":"We thank Prof. Masazumi Tada and Roland Dosch for providing transgenic zebrafish lines, the Heisenberg lab for technical assistance and feedback on the manuscript, and the Bioimaging and Fish facilities of IST Austria for continuous support. This work was funded by an ERC advanced grant (MECSPEC to C.-P.H.).","external_id":{"pmid":["33606227"]},"citation":{"chicago":"Xia, Peng, and Carl-Philipp J Heisenberg. “Quantifying Tissue Tension in the Granulosa Layer after Laser Surgery.” In <i>Germline Development in the Zebrafish</i>, edited by Roland Dosch, 2218:117–28. Humana, 2021. <a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">https://doi.org/10.1007/978-1-0716-0970-5_10</a>.","ieee":"P. Xia and C.-P. J. Heisenberg, “Quantifying tissue tension in the granulosa layer after laser surgery,” in <i>Germline Development in the Zebrafish</i>, vol. 2218, R. Dosch, Ed. Humana, 2021, pp. 117–128.","apa":"Xia, P., &#38; Heisenberg, C.-P. J. (2021). Quantifying tissue tension in the granulosa layer after laser surgery. In R. Dosch (Ed.), <i>Germline Development in the Zebrafish</i> (Vol. 2218, pp. 117–128). Humana. <a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">https://doi.org/10.1007/978-1-0716-0970-5_10</a>","ama":"Xia P, Heisenberg C-PJ. Quantifying tissue tension in the granulosa layer after laser surgery. In: Dosch R, ed. <i>Germline Development in the Zebrafish</i>. Vol 2218. Humana; 2021:117-128. doi:<a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">10.1007/978-1-0716-0970-5_10</a>","ista":"Xia P, Heisenberg C-PJ. 2021.Quantifying tissue tension in the granulosa layer after laser surgery. In: Germline Development in the Zebrafish. Methods in Molecular Biology, vol. 2218, 117–128.","short":"P. Xia, C.-P.J. Heisenberg, in:, R. Dosch (Ed.), Germline Development in the Zebrafish, Humana, 2021, pp. 117–128.","mla":"Xia, Peng, and Carl-Philipp J. Heisenberg. “Quantifying Tissue Tension in the Granulosa Layer after Laser Surgery.” <i>Germline Development in the Zebrafish</i>, edited by Roland Dosch, vol. 2218, Humana, 2021, pp. 117–28, doi:<a href=\"https://doi.org/10.1007/978-1-0716-0970-5_10\">10.1007/978-1-0716-0970-5_10</a>."},"year":"2021","date_updated":"2022-06-03T10:57:55Z","abstract":[{"text":"Tissue morphogenesis is driven by mechanical forces triggering cell movements and shape changes. Quantitatively measuring tension within tissues is of great importance for understanding the role of mechanical signals acting on the cell and tissue level during morphogenesis. Here we introduce laser ablation as a useful tool to probe tissue tension within the granulosa layer, an epithelial monolayer of somatic cells that surround the zebrafish female gamete during folliculogenesis. We describe in detail how to isolate follicles, mount samples, perform laser surgery, and analyze the data.","lang":"eng"}],"day":"20","doi":"10.1007/978-1-0716-0970-5_10"},{"publication_identifier":{"eissn":["2050-084X"]},"oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2021-08-27T00:00:00Z","file":[{"date_created":"2022-05-13T08:03:37Z","checksum":"a3f82b0499cc822ac1eab48a01f3f57e","file_size":9010446,"date_updated":"2022-05-13T08:03:37Z","content_type":"application/pdf","file_name":"2021_eLife_Pulgar.pdf","success":1,"relation":"main_file","access_level":"open_access","file_id":"11371","creator":"dernst"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","project":[{"call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"}],"oa_version":"Published Version","article_number":"e66483","month":"08","has_accepted_license":"1","publication":"eLife","keyword":["cell delamination","apical constriction","dragging","mechanical forces","collective 18 locomotion","dorsal forerunner cells","zebrafish"],"language":[{"iso":"eng"}],"day":"27","doi":"10.7554/eLife.66483","abstract":[{"text":"The developmental strategies used by progenitor cells to endure a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a progenitor cell allocation mechanism that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the surface epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-term apical contacts that enable the epithelial layer to pull a subset of progenitors along their way towards the vegetal pole. The remaining delaminated progenitors follow apically-attached progenitors’ movement by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm, ensuring their fate and collective allocation at the differentiation site. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development. Impact Statement: Incomplete delamination serves as a cellular platform for coordinated tissue movements during development, guiding newly formed progenitor cell groups to the differentiation site.","lang":"eng"}],"citation":{"chicago":"Pulgar, Eduardo, Cornelia Schwayer, Néstor Guerrero, Loreto López, Susana Márquez, Steffen Härtel, Rodrigo Soto, Carl Philipp Heisenberg, and Miguel L. Concha. “Apical Contacts Stemming from Incomplete Delamination Guide Progenitor Cell Allocation through a Dragging Mechanism.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.66483\">https://doi.org/10.7554/eLife.66483</a>.","ieee":"E. Pulgar <i>et al.</i>, “Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","ama":"Pulgar E, Schwayer C, Guerrero N, et al. Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.66483\">10.7554/eLife.66483</a>","apa":"Pulgar, E., Schwayer, C., Guerrero, N., López, L., Márquez, S., Härtel, S., … Concha, M. L. (2021). Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.66483\">https://doi.org/10.7554/eLife.66483</a>","ista":"Pulgar E, Schwayer C, Guerrero N, López L, Márquez S, Härtel S, Soto R, Heisenberg CP, Concha ML. 2021. Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism. eLife. 10, e66483.","short":"E. Pulgar, C. Schwayer, N. Guerrero, L. López, S. Márquez, S. Härtel, R. Soto, C.P. Heisenberg, M.L. Concha, ELife 10 (2021).","mla":"Pulgar, Eduardo, et al. “Apical Contacts Stemming from Incomplete Delamination Guide Progenitor Cell Allocation through a Dragging Mechanism.” <i>ELife</i>, vol. 10, e66483, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.66483\">10.7554/eLife.66483</a>."},"year":"2021","date_updated":"2023-08-14T06:53:33Z","external_id":{"isi":["000700428500001"],"pmid":["34448451"]},"isi":1,"volume":10,"ddc":["570"],"department":[{"_id":"CaHe"}],"date_created":"2021-09-12T22:01:23Z","article_processing_charge":"Yes","publication_status":"published","intvolume":"        10","title":"Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism","scopus_import":"1","pmid":1,"_id":"9999","author":[{"full_name":"Pulgar, Eduardo","first_name":"Eduardo","last_name":"Pulgar"},{"id":"3436488C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwayer, Cornelia","orcid":"0000-0001-5130-2226","last_name":"Schwayer","first_name":"Cornelia"},{"full_name":"Guerrero, Néstor","first_name":"Néstor","last_name":"Guerrero"},{"full_name":"López, Loreto","first_name":"Loreto","last_name":"López"},{"full_name":"Márquez, Susana","first_name":"Susana","last_name":"Márquez"},{"last_name":"Härtel","first_name":"Steffen","full_name":"Härtel, Steffen"},{"first_name":"Rodrigo","last_name":"Soto","full_name":"Soto, Rodrigo"},{"last_name":"Heisenberg","first_name":"Carl Philipp","full_name":"Heisenberg, Carl Philipp"},{"first_name":"Miguel L.","last_name":"Concha","full_name":"Concha, Miguel L."}],"publisher":"eLife Sciences Publications","article_type":"original","ec_funded":1,"quality_controlled":"1","file_date_updated":"2022-05-13T08:03:37Z"}]