{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:46:12Z","timestamp":1790711172606,"version":"4.1.0"},"reference-count":21,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,15]]},"abstract":"<jats:p>\n                    Mutation in human ZIC2, a zinc finger protein homologous to\n                    <jats:italic>Drosophila<\/jats:italic>\n                    odd-paired, causes holoprosencephaly (HPE), which is a common, severe malformation of the brain in humans. However, the pathogenesis is largely unknown. Here we show that reduced expression (knockdown) of mouse\n                    <jats:italic>Zic2<\/jats:italic>\n                    causes neurulation delay, resulting in HPE and spina bifida. Differentiation of the most dorsal neural plate, which gives rise to both roof plate and neural crest cells, also was delayed as indicated by the expression lag of a roof plate marker,\n                    <jats:italic>Wnt3a<\/jats:italic>\n                    . In addition the development of neural crest derivatives such as dorsal root ganglion was impaired. These results suggest that the\n                    <jats:italic>Zic2<\/jats:italic>\n                    expression level is crucial for the timing of neurulation. Because the\n                    <jats:italic>Zic2<\/jats:italic>\n                    knockdown mouse is the first mutant with HPE and spina bifida to survive to the perinatal period, the mouse will promote analyses of not only the neurulation but also the pathogenesis of human HPE.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.4.1618","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"1618-1623","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":216,"title":["Zic2 regulates the kinetics of neurulation"],"prefix":"10.1073","volume":"97","author":[{"given":"Takeharu","family":"Nagai","sequence":"first","affiliation":[{"name":"Molecular Neurobiology Laboratory, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; Developmental Neurobiology Laboratory, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; Division of Research Facilitation, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8577, Japan; and Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Aruga","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Laboratory, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; Developmental Neurobiology Laboratory, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; Division of Research Facilitation, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8577, Japan; and Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Minowa","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Laboratory, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; Developmental Neurobiology Laboratory, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; Division of Research Facilitation, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8577, Japan; and Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Laboratory, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; Developmental Neurobiology Laboratory, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; Division of Research Facilitation, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8577, Japan; and Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Ohno","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Laboratory, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; Developmental Neurobiology Laboratory, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; Division of Research Facilitation, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8577, Japan; and Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Noda","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Laboratory, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; Developmental Neurobiology Laboratory, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; Division of Research Facilitation, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8577, Japan; and Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Mikoshiba","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Laboratory, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; Developmental Neurobiology Laboratory, Brain Science Institute, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; Division of Research Facilitation, University of Tsukuba, Tsukuba-shi, Ibaraki 305-8577, Japan; and Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,2,15]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"19","volume":"39","author":"Edmonds L D","year":"1990","unstructured":"L D Edmonds, L M James Morbid Mortal Wkly Rep 39, 19\u201323 (1990).","journal-title":"Morbid Mortal Wkly Rep"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1998.tb02666.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/2484"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.1.105"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.1043"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.8449"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-01-00284.1998"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2980275"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0291"},{"key":"e_1_3_3_10_2","volume-title":"Manipulating the Mouse Embryo","author":"Hogan B","year":"1994","unstructured":"B Hogan, R Beddington, F Constantini, E Lacy Manipulating the Mouse Embryo (Cold Spring Harbor Lab. 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