{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:56:32Z","timestamp":1791950192567,"version":"4.3.4"},"reference-count":59,"publisher":"Cold Spring Harbor Laboratory","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2001,12,1]]},"abstract":"<jats:p>\n                    Mutations in the homeobox gene\n                    <jats:italic>vHnf1<\/jats:italic>\n                    are associated with human diseases MODY5 (maturity-onset diabetes of the young, type V) and familial GCKD (glomerulocystic kidney disease). In an insertional mutagenesis screen in zebrafish, we isolated mutant alleles of\n                    <jats:italic>vhnf1<\/jats:italic>\n                    . Phenotypes of these mutants include formation of kidney cysts, underdevelopment of the pancreas and the liver, and reduction in size of the otic vesicles. We show that these abnormalities arise from patterning defects during development. We further provide evidence that\n                    <jats:italic>vhnf1<\/jats:italic>\n                    regulates the expression of key patterning genes for these organs.\n                    <jats:italic>vhnf1<\/jats:italic>\n                    is required for the proper expression of\n                    <jats:italic>pdx1<\/jats:italic>\n                    and\n                    <jats:italic>shh<\/jats:italic>\n                    (\n                    <jats:italic>sonic hedgehog<\/jats:italic>\n                    ) in the gut endoderm,\n                    <jats:italic>pax2<\/jats:italic>\n                    and\n                    <jats:italic>wt1<\/jats:italic>\n                    in the pronephric primordial, and\n                    <jats:italic>valentino<\/jats:italic>\n                    (\n                    <jats:italic>val<\/jats:italic>\n                    ) in the hindbrain. Complementary to the loss-of-function phenotypes, overexpression of\n                    <jats:italic>vhnf1<\/jats:italic>\n                    induces expansion of the\n                    <jats:italic>val<\/jats:italic>\n                    expression domain in the hindbrain. We propose that\n                    <jats:italic>vhnf1<\/jats:italic>\n                    controls development of multiple organs through regulating regional specification of organ primordia. The similarity between\n                    <jats:italic>vhnf1<\/jats:italic>\n                    -associated fish phenotypes and human symptoms suggests a correlation between developmental functions of\n                    <jats:italic>vhnf1<\/jats:italic>\n                    and the molecular etiology of MODY5 and GCKD.\n                  <\/jats:p>","DOI":"10.1101\/gad946701","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:59:15Z","timestamp":1027713555000},"page":"3217-3229","source":"Crossref","is-referenced-by-count":189,"title":["<i>vhnf1<\/i>\n                    , the MODY5 and familial GCKD-associated gene, regulates regional specification of the zebrafish gut, pronephros, and hindbrain"],"prefix":"10.1101","volume":"15","author":[{"given":"Zhaoxia","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2001,12,1]]},"reference":[{"key":"2021111507523832000_15.23.3217.1","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1242\/dev.119.4.1301","article-title":"The formation and maintenance of the definitive endoderm lineage in the mouse: Involvement of HNF3\/forkhead proteins.","volume":"119","author":"Ang","year":"1993","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(06)00340-X"},{"key":"2021111507523832000_15.23.3217.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00151-3"},{"key":"2021111507523832000_15.23.3217.4","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(93)90090-K"},{"key":"2021111507523832000_15.23.3217.5","doi-asserted-by":"crossref","first-page":"4795","DOI":"10.1242\/dev.126.21.4795","article-title":"Variant hepatocyte nuclear factor 1 is required for visceral endoderm specification.","volume":"126","author":"Barbacci","year":"1999","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009088200"},{"key":"2021111507523832000_15.23.3217.7","doi-asserted-by":"publisher","DOI":"10.1086\/316945"},{"key":"2021111507523832000_15.23.3217.8","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90592-3"},{"key":"2021111507523832000_15.23.3217.9","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1242\/dev.116.3.783","article-title":"Expression patterns of vHNF1 and HNF1 homeoproteins in early postimplantation embryos suggest distinct and sequential developmental roles.","volume":"116","author":"Cereghini","year":"1992","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.10","doi-asserted-by":"crossref","first-page":"4785","DOI":"10.1242\/dev.126.21.4785","article-title":"Essential role for the homeoprotein vHNF1\/HNF1beta in visceral endoderm differentiation.","volume":"126","author":"Coffinier","year":"1999","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.11","first-page":"263","article-title":"Transcription factors in renal development: The WT1 and Pax-2 story.","volume":"15","author":"Dressler","year":"1995","journal-title":"Semin. Nephrol."},{"key":"2021111507523832000_15.23.3217.12","doi-asserted-by":"publisher","DOI":"10.1007\/s004670050788"},{"key":"2021111507523832000_15.23.3217.13","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.1242\/dev.125.23.4655","article-title":"Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function.","volume":"125","author":"Drummond","year":"1998","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.14","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.1999.560101.x"},{"key":"2021111507523832000_15.23.3217.15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0300-9084(91)90079-G","article-title":"Krox-20: A candidate gene for the regulation of pattern formation in the hindbrain.","volume":"73","author":"Gilardi","year":"1991","journal-title":"Biochimie"},{"key":"2021111507523832000_15.23.3217.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01957-5"},{"key":"2021111507523832000_15.23.3217.17","doi-asserted-by":"publisher","DOI":"10.1101\/gad.846001"},{"key":"2021111507523832000_15.23.3217.18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1242\/dev.121.1.11","article-title":"Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny.","volume":"121","author":"Guz","year":"1995","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.19","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90008-T"},{"key":"2021111507523832000_15.23.3217.20","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.11.1705"},{"key":"2021111507523832000_15.23.3217.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-384"},{"key":"2021111507523832000_15.23.3217.22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3109\/10520297409116929","article-title":"A simple methylene blue-azure II-basic fuchsin stain for epoxy-embedded tissue sections.","volume":"49","author":"Humphrey","year":"1974","journal-title":"Stain Technology"},{"key":"2021111507523832000_15.23.3217.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.13036"},{"key":"2021111507523832000_15.23.3217.24","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002030302"},{"key":"2021111507523832000_15.23.3217.25","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1242\/dev.113.4.1193","article-title":"Expression of the zebrafish paired box gene pax[zf-b] during early neurogenesis.","volume":"113","author":"Krauss","year":"1991","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.26","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90628-4"},{"key":"2021111507523832000_15.23.3217.27","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90515-R"},{"key":"2021111507523832000_15.23.3217.28","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1242\/dev.114.2.469","article-title":"LFB1 and LFB3 homeoproteins are sequentially expressed during kidney development.","volume":"114","author":"Lazzaro","year":"1992","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.29","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1242\/dev.127.20.4303","article-title":"Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish.","volume":"127","author":"Liao","year":"2000","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.30","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.11.2001"},{"key":"2021111507523832000_15.23.3217.31","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1242\/dev.127.10.2089","article-title":"Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia.","volume":"127","author":"Majumdar","year":"2000","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.32","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1242\/dev.127.11.2433","article-title":"The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation.","volume":"127","author":"Martinez Barbera","year":"2000","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.33","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1242\/dev.125.3.381","article-title":"Equivalence in the genetic control of hindbrain segmentation in fish and mouse.","volume":"125","author":"Moens","year":"1998","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.34","doi-asserted-by":"publisher","DOI":"10.2337\/diab.47.8.1354"},{"key":"2021111507523832000_15.23.3217.35","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1242\/dev.122.3.983","article-title":"PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum.","volume":"122","author":"Offield","year":"1996","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.36","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1412"},{"key":"2021111507523832000_15.23.3217.37","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(91)90071-D"},{"key":"2021111507523832000_15.23.3217.38","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/21.5.1087"},{"key":"2021111507523832000_15.23.3217.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.2931"},{"key":"2021111507523832000_15.23.3217.40","doi-asserted-by":"publisher","DOI":"10.1038\/353431a0"},{"key":"2021111507523832000_15.23.3217.41","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0297"},{"key":"2021111507523832000_15.23.3217.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81033-8"},{"key":"2021111507523832000_15.23.3217.43","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1242\/dev.125.3.393","article-title":"Zebrafish hox genes: Expression in the hindbrain region of wild-type and mutants of the segmentation gene, valentino.","volume":"125","author":"Prince","year":"1998","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.44","doi-asserted-by":"publisher","DOI":"10.1038\/346194a0"},{"key":"2021111507523832000_15.23.3217.45","first-page":"1023","article-title":"Expression of the Wilms' tumor suppressor gene WT1 during mouse embryogenesis.","volume":"4","author":"Rackley","year":"1993","journal-title":"Cell Growth Differ."},{"key":"2021111507523832000_15.23.3217.46","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/j.1460-2075.1991.tb07665.x","article-title":"vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1.","volume":"10","author":"Rey-Campos","year":"1991","journal-title":"EMBO J."},{"key":"2021111507523832000_15.23.3217.47","first-page":"263","article-title":"Familial hypoplastic glomerulocystic kidney. A new entity?","volume":"18","author":"Rizzoni","year":"1982","journal-title":"Clin. Nephrol."},{"key":"2021111507523832000_15.23.3217.48","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1242\/dev.119.3.711","article-title":"Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development.","volume":"119","author":"Rothenpieler","year":"1993","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.49","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00402-X"},{"key":"2021111507523832000_15.23.3217.50","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1242\/dev.128.12.2233","article-title":"Pre-pattern in the pronephric kidney field of zebrafish.","volume":"128","author":"Serluca","year":"2001","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.51","doi-asserted-by":"publisher","DOI":"10.1038\/86871"},{"key":"2021111507523832000_15.23.3217.52","doi-asserted-by":"publisher","DOI":"10.1038\/ng1097-138"},{"key":"2021111507523832000_15.23.3217.53","first-page":"929","article-title":"Expression of axial and sonic hedgehog in wildtype and midline defective zebrafish embryos.","volume":"40","author":"Strahle","year":"1996","journal-title":"Int. J. Dev. Biol."},{"key":"2021111507523832000_15.23.3217.54","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1242\/dev.121.12.4057","article-title":"Pax-2 controls multiple steps of urogenital development.","volume":"121","author":"Torres","year":"1995","journal-title":"Development"},{"key":"2021111507523832000_15.23.3217.55","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950140902"},{"key":"2021111507523832000_15.23.3217.56","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90523-1"},{"key":"2021111507523832000_15.23.3217.57","unstructured":"Westerfield M. (1993) The Zebrafish book: A guide for the laboratory use of zebrafish (brachydanio rerio). (The University of Oregon Press, Eugene, OR)."},{"key":"2021111507523832000_15.23.3217.58","doi-asserted-by":"publisher","DOI":"10.1038\/384455a0"},{"key":"2021111507523832000_15.23.3217.59","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00204-4"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad946701","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T10:54:44Z","timestamp":1636973684000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad946701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12,1]]},"references-count":59,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2001,12,1]]}},"alternative-id":["10.1101\/gad946701"],"URL":"https:\/\/doi.org\/10.1101\/gad946701","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1003684.40405","asserted-by":"object"}]},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,12,1]]}}}