{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:32:10Z","timestamp":1791271930764,"version":"4.1.0"},"reference-count":29,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5752","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2005,11,25]]},"abstract":"\n Cell-cell interactions and cross-talk between signaling pathways specify\n Caenorhabditis elegans<\/jats:italic>\n vulval precursor cells (VPCs) to adopt a spatial pattern: a central \u201c1\u00b0\u201d VPC, in which epidermal growth factor receptor (EGFR)\u2013mitogen-activated protein kinase (MAPK) activity is high and LIN-12\/Notch activity is low, flanked by two \u201c2\u00b0\u201d VPCs, in which LIN-12\/Notch activity is high and EGFR-MAPK activity is low. Here, we identify a microRNA gene,\n mir-61<\/jats:italic>\n , as a direct transcriptional target of LIN-12 and show that expression of\n mir-61<\/jats:italic>\n promotes the 2\u00b0 fate. We also identify\n vav-1<\/jats:italic>\n , the ortholog of the Vav oncogene, as a target of\n mir-61<\/jats:italic>\n , and show that down-regulation of VAV-1 promotes\n lin-12<\/jats:italic>\n activity in specifying the 2\u00b0 fate. Our results suggest that\n lin-12, mir-61<\/jats:italic>\n , and\n vav-1<\/jats:italic>\n form a feedback loop that helps maximize\n lin-12<\/jats:italic>\n activity in the presumptive 2\u00b0 VPCs.\n <\/jats:p>","DOI":"10.1126\/science.1119481","type":"journal-article","created":{"date-parts":[[2005,10,26]],"date-time":"2005-10-26T03:33:44Z","timestamp":1130297624000},"page":"1330-1333","source":"Crossref","is-referenced-by-count":132,"title":["LIN-12\/Notch Activation Leads to MicroRNA-Mediated Down-Regulation of Vav in\n C. elegans<\/i>"],"prefix":"10.1126","volume":"310","author":[{"given":"Andrew S.","family":"Yoo","sequence":"first","affiliation":[{"name":"Integrated Program in Cellular, Molecular, and Biophysical Studies, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, 701 West 168th Street, Room 720, New York, NY 10032, USA."},{"name":"Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, 701 West 168th Street, Room 720, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Greenwald","sequence":"additional","affiliation":[{"name":"Integrated Program in Cellular, Molecular, and Biophysical Studies, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, 701 West 168th Street, Room 720, New York, NY 10032, USA."},{"name":"Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, 701 West 168th Street, Room 720, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","unstructured":"P. W. Sternberg in WormBook (2005) (www.wormbook.org)."},{"key":"e_1_3_1_3_2","unstructured":"I. Greenwald in WormBook (2005) (www.wormbook.org)."},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1091639"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90529-Y"},{"key":"e_1_3_1_6_2","unstructured":"Supporting Online Material is available on Science Online."},{"key":"e_1_3_1_7_2","unstructured":"All transcriptional reporters were made by polymerase chain reaction (PCR) fusion from the predicted start to the next predicted upstream gene and extra-chromosomal arrays were marked with pha-1(+) . Expression of mir-61 transcription was studied by using the arIs107 integrant which displayed the same pattern as extrachromosomal arrays."},{"key":"e_1_3_1_8_2","unstructured":"mir-61 is also expressed in cells of the somatic gonad in which LIN-12 is active and this expression is also lost when the LBSs are mutated (Fig. 1 B and C). In contrast expression in other tissues where we have no evidence that lin-12 activity is functionally relevant such as intestinal cells is unaffected. These observations suggest that the loss of expression in P5.p and P7.p reflects lack of response to lin-12 and not loss of a general enhancer."},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02871"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1091903"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02752"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.16.2623"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5462-03.2004"},{"key":"e_1_3_1_14_2","unstructured":"We used two separate arrays because of possible promoter interference that we have experienced when using the same promoter to drive two different gene products in the same array. For the assessment of many targets the assay could be improved by integrating the transgene expressing the miRNA."},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90377-X"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2005.04.003"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.001"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/135.3.765"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3182"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.145.6.1165"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.03.019"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/35084096"},{"key":"e_1_3_1_23_2","unstructured":"A. S. Yoo unpublished observations."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152320899"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.6.1083"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02255"},{"key":"e_1_3_1_27_2","unstructured":"From pPD95.67 gift of A. Fire (Stanford University)."},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00021-8"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02076"},{"key":"e_1_3_1_30_2","unstructured":"We are grateful to X. Zhou for performing microinjections; and to O. Hobert R. Mann and D. Shaye for discussion and insightful comments on the manuscript. This work was supported by NIH grant CA095389 (to I.G.). I.G. is an investigator with the Howard Hughes Medical Institute."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1119481","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:09:38Z","timestamp":1704834578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1119481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,25]]},"references-count":29,"journal-issue":{"issue":"5752","published-print":{"date-parts":[[2005,11,25]]}},"alternative-id":["10.1126\/science.1119481"],"URL":"https:\/\/doi.org\/10.1126\/science.1119481","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1028699.342290","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1028699.343657","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,25]]}}}