{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:23:33Z","timestamp":1791325413473,"version":"4.3.1"},"reference-count":32,"publisher":"The Company of Biologists","issue":"24","license":[{"start":{"date-parts":[[1999,12,15]],"date-time":"1999-12-15T00:00:00Z","timestamp":945216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pitx2, a bicoid-related homeobox gene, is involved in Rieger\u2019s syndrome and the left-right (L-R) asymmetrical pattern formation in body plan. In order to define the genomic structure and roles of Pitx2, we analyzed the genomic structure and generated Pitx2-deficient mice with the lacZ gene in the homeobox-containing exon of Pitx2. We were able to show that among three isoforms of Pitx2, Pitx2c shows asymmetrical expression whereas Pitx2a, Pitx2b and Pitx2c show symmetrical expression. In Pitx2\u2212\/\u2212 embryos there was an increase in mesodermal cells in the distal end of the left lateral body wall and an amnion continuous with the lateral body wall thickened in its mesodermal layer. These changes resulted in a failure of ventral body wall closure. In lung and heart in which Pitx2 is expressed asymmetrically, right pulmonary isomerism, atrioventricular canals with prominent swelling, and juxtaposition of the atrium were detected. The hearts failed to develop tricuspid and mitral valves and a common atrioventricular valve forms. Further, dysgenesis of the Pitx2\u2212\/\u2212 extraocular muscle and thickening of the mesothelial layer of cornea were observed in the ocular system where Pitx2 is expressed symmetrically, and these resulted in enophthalmos. The present study shows that Pitx2 expressed in various sites participates in morphogenesis through three types of actions: the involvement of asymmetric Pitx2 expression in the entire morphogenetic process of L-R asymmetric organs; the involvement of asymmetric Pitx2 expression in the regional morphogenesis of asymmetric organs; and finally the involvement of symmetric Pitx2 expression in the regional morphogenesis of symmetric organs.<\/jats:p>","DOI":"10.1242\/dev.126.24.5749","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:58:00Z","timestamp":1619409480000},"page":"5749-5758","source":"Crossref","is-referenced-by-count":415,"title":["Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism"],"prefix":"10.1242","volume":"126","author":[{"given":"Kunio","family":"Kitamura","sequence":"first","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Miura","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Miyagawa-Tomita","sequence":"additional","affiliation":[{"name":"Tokyo Women\u2019s Medical University 2 Department of Pediatric Cardiology, The Heart Institute of Japan , , 8-1 Kawada-cho, Shinjuku- ku, Tokyo 162-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Yanazawa","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Katoh-Fukui","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Suzuki","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyo","family":"Ohuchi","sequence":"additional","affiliation":[{"name":"Kyoto University Graduate School of Pharmaceutical Sciences 3 Department of Genetic Biochemistry, Faculty of Pharmaceutical Sciences , , Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atuko","family":"Suehiro","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Motegi","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Nakahara","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunzo","family":"Kondo","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minesuke","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"1 Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,12,15]]},"reference":[{"key":"2023090608070473900_DEVELOP_126_24_5749C1","doi-asserted-by":"publisher","first-page":"4867","DOI":"10.1242\/dev.124.23.4867","article-title":"Fibroblast growth factor 10 (FGF10) and branching morophogenesis in the embryonic mouse lung","volume":"124","author":"Bellusci","year":"1997","journal-title":"Development"},{"key":"2023090608070473900_DEVELOP_126_24_5749C2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/BF02401419","article-title":"Polymorphisms in the coding and noncoding regions of murine Pgk-1 alles","volume":"28","author":"Boer","year":"1990","journal-title":"Biochem. 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