{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:57:19Z","timestamp":1791046639408,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Developmental Biology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["PCEFP3_181204"],"award-info":[{"award-number":["PCEFP3_181204"]}],"id":[{"id":"https:\/\/ror.org\/00yjd3n13","id-type":"ROR","asserted-by":"publisher"}]},{"award":["310030_219822"],"award-info":[{"award-number":["310030_219822"]}],"id":[{"id":"https:\/\/ror.org\/00yjd3n13","id-type":"ROR","asserted-by":"publisher"}]},{"award":["320030L-227534"],"award-info":[{"award-number":["320030L-227534"]}],"id":[{"id":"https:\/\/ror.org\/00yjd3n13","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Novartis Foundation","award":["20A011"],"award-info":[{"award-number":["20A011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Maintaining appropriate organ size ratios in the face of growth fluctuations is critical for the development of a reproducible body plan. Yet the mechanisms involved remain poorly understood. Here, we investigated how pharynx-to-body proportions are maintained in\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  , combining tissue-specific perturbations, genetic screening, and longitudinal live imaging. A genome-wide RNAi screen revealed that knock-down of the dual-specificity MAPK phosphatase VHP-1 turns animals hypersensitive to inter-tissue growth imbalance caused by pharyngeal or epidermal depletion of the mTORC1 activator RAGA-1 or the ribosomal protein RPL-22. In contrast,\n                  <jats:italic>vhp-1<\/jats:italic>\n                  mutants tolerated global\n                  <jats:italic>raga-1<\/jats:italic>\n                  loss, indicating a specific requirement for\n                  <jats:italic>vhp-1<\/jats:italic>\n                  under tissue growth imbalance. Knock-down of the p38 pathway suppressed the imbalance-specific defects of\n                  <jats:italic>vhp-1<\/jats:italic>\n                  mutants. In contrast, JNK knock-down effectively rescued the pleiotropic phenotypes of\n                  <jats:italic>vhp-1<\/jats:italic>\n                  mutants but only weakly reduced their sensitivity to RAGA-1 imbalance, indicating that these two stress-MAPK pathways make distinct contributions to the response to growth imbalance. Finally, whole-animal VHP-1 levels increased upon epidermal RAGA-1 depletion, and epidermal VHP-1 depletion did not reproduce the sensitivity caused by global\n                  <jats:italic>vhp-1<\/jats:italic>\n                  loss, consistent with a contribution from VHP-1 outside the growth-perturbed epidermis in buffering against local growth imbalance.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary statement<\/jats:title>\n                  <jats:p>\n                    The MAPK phosphatase VHP-1 is critical for buffering\n                    <jats:italic>C. elegans<\/jats:italic>\n                    development against tissue growth imbalance.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>New<\/jats:title>\n                    <jats:p>imbalance-vs-slow-growth dissociation, non-autonomy of VHP-1, splitting p38 from JNK functionally, endogenous VHP-1 dynamics.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.28.754458","type":"posted-content","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:00:33Z","timestamp":1790694033000},"source":"Crossref","is-referenced-by-count":0,"title":["The MAPK phosphatase VHP-1 buffers pharynx-to-body proportions against tissue-specific growth imbalance in\n                  <i>C. elegans<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4600-0954","authenticated-orcid":false,"given":"Ioana","family":"Gheorghe","sequence":"first","affiliation":[{"name":"University of Bern, Institute of Cell Biology, Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klement","family":"Stojanovski","sequence":"additional","affiliation":[{"name":"University of Bern, Institute of Cell Biology, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7330-6882","authenticated-orcid":false,"given":"Delia","family":"Bogenst\u00e4tter","sequence":"additional","affiliation":[{"name":"University of Bern, Institute of Cell Biology, Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8325-8502","authenticated-orcid":false,"given":"Anna","family":"Graf","sequence":"additional","affiliation":[{"name":"University of Bern, Institute of Cell Biology, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Beuchle","sequence":"additional","affiliation":[{"name":"University of Bern, Institute of Cell Biology, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1844-6679","authenticated-orcid":false,"given":"Sacha","family":"Psalmon","sequence":"additional","affiliation":[{"name":"University of Bern, Institute of Cell Biology, Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-1257","authenticated-orcid":false,"given":"Benjamin Daniel","family":"Towbin","sequence":"additional","affiliation":[{"name":"University of Bern, Institute of Cell Biology, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100309500683000_2026.09.28.754458v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.03.005"},{"key":"2026100309500683000_2026.09.28.754458v1.2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.711101"},{"key":"2026100309500683000_2026.09.28.754458v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyab006"},{"key":"2026100309500683000_2026.09.28.754458v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0582-9"},{"key":"2026100309500683000_2026.09.28.754458v1.5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00347.2009"},{"key":"2026100309500683000_2026.09.28.754458v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33387-6"},{"key":"2026100309500683000_2026.09.28.754458v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13505"},{"key":"2026100309500683000_2026.09.28.754458v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.03.016"},{"key":"2026100309500683000_2026.09.28.754458v1.9","doi-asserted-by":"publisher","DOI":"10.1242\/dev.196063"},{"key":"2026100309500683000_2026.09.28.754458v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15213"},{"key":"2026100309500683000_2026.09.28.754458v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.01.019"},{"key":"2026100309500683000_2026.09.28.754458v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80362-7"},{"key":"2026100309500683000_2026.09.28.754458v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.09.020"},{"key":"2026100309500683000_2026.09.28.754458v1.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1216689"},{"key":"2026100309500683000_2026.09.28.754458v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.07.014"},{"key":"2026100309500683000_2026.09.28.754458v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21611-8"},{"key":"2026100309500683000_2026.09.28.754458v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.042"},{"key":"2026100309500683000_2026.09.28.754458v1.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1216735"},{"key":"2026100309500683000_2026.09.28.754458v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9732"},{"key":"2026100309500683000_2026.09.28.754458v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2016.07.016"},{"key":"2026100309500683000_2026.09.28.754458v1.21","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.181"},{"key":"2026100309500683000_2026.09.28.754458v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12500"},{"key":"2026100309500683000_2026.09.28.754458v1.23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204270200"},{"key":"2026100309500683000_2026.09.28.754458v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/nature01278"},{"key":"2026100309500683000_2026.09.28.754458v1.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403546101"},{"key":"2026100309500683000_2026.09.28.754458v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2004.11.012"},{"key":"2026100309500683000_2026.09.28.754458v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605711"},{"key":"2026100309500683000_2026.09.28.754458v1.28","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1319"},{"key":"2026100309500683000_2026.09.28.754458v1.29","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301446"},{"key":"2026100309500683000_2026.09.28.754458v1.30","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.4.557"},{"key":"2026100309500683000_2026.09.28.754458v1.31","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.20.6999-7009.2001"},{"key":"2026100309500683000_2026.09.28.754458v1.32","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111895"},{"key":"2026100309500683000_2026.09.28.754458v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600226"},{"key":"2026100309500683000_2026.09.28.754458v1.34","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.164202"},{"key":"2026100309500683000_2026.09.28.754458v1.35","unstructured":"Murphy, C.T. and Hu, P.J. (2018) \u201cInsulin\/insulin-like growth factor signaling in C. elegans,\u201d WormBook: The Online Review of C. elegans Biology [Internet]. WormBook. Available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK179230\/ (Accessed: August 7, 2026)."},{"key":"2026100309500683000_2026.09.28.754458v1.36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.535245"},{"key":"2026100309500683000_2026.09.28.754458v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/40194"},{"key":"2026100309500683000_2026.09.28.754458v1.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500749102"},{"key":"2026100309500683000_2026.09.28.754458v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.07.002"},{"key":"2026100309500683000_2026.09.28.754458v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.039"},{"key":"2026100309500683000_2026.09.28.754458v1.41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005086"},{"key":"2026100309500683000_2026.09.28.754458v1.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008133"},{"key":"2026100309500683000_2026.09.28.754458v1.43","doi-asserted-by":"publisher","DOI":"10.1534\/g3.119.400314"},{"key":"2026100309500683000_2026.09.28.754458v1.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010938"},{"key":"2026100309500683000_2026.09.28.754458v1.45","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.6.1091"},{"key":"2026100309500683000_2026.09.28.754458v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43230-1"},{"key":"2026100309500683000_2026.09.28.754458v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29720-8"},{"key":"2026100309500683000_2026.09.28.754458v1.48","doi-asserted-by":"publisher","DOI":"10.1534\/g3.112.003830"},{"key":"2026100309500683000_2026.09.28.754458v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.01.005"},{"key":"2026100309500683000_2026.09.28.754458v1.50","doi-asserted-by":"publisher","DOI":"10.3791\/52742"},{"key":"2026100309500683000_2026.09.28.754458v1.51","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00829.x"},{"key":"2026100309500683000_2026.09.28.754458v1.52","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac6767"},{"key":"2026100309500683000_2026.09.28.754458v1.53","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.391"},{"key":"2026100309500683000_2026.09.28.754458v1.54","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.170190"},{"key":"2026100309500683000_2026.09.28.754458v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.03.015"},{"key":"2026100309500683000_2026.09.28.754458v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40317-7"},{"key":"2026100309500683000_2026.09.28.754458v1.57","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129635"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.28.754458","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:50:14Z","timestamp":1791046214000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.28.754458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":57,"URL":"https:\/\/doi.org\/10.64898\/2026.09.28.754458","relation":{},"subject":[],"published":{"date-parts":[[2026,9,29]]},"subtype":"preprint"}}