{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:21:25Z","timestamp":1790814085971,"version":"4.1.0"},"reference-count":48,"publisher":"The Company of Biologists","issue":"23","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":182,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY12162"],"award-info":[{"award-number":["EY12162"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Holoprosencephaly (HPE) is defined as the incomplete separation of the two cerebral hemispheres. The pathology of HPE is variable and, based on the severity of the defect, HPE is divided into alobar, semilobar, and lobar. Using a novel hypomorphic Six3 allele, we demonstrate in mice that variability in Six3 dosage results in different HPE phenotypes. Furthermore, we show that whereas the semilobar phenotype results from severe downregulation of Shh expression in the rostral diencephalon ventral midline, the alobar phenotype is caused by downregulation of Foxg1 expression in the anterior neural ectoderm. Consistent with these results, in vivo activation of the Shh signaling pathway rescued the semilobar phenotype but not the alobar phenotype. Our findings show that variations in Six3 dosage result in different forms of HPE.<\/jats:p>","DOI":"10.1242\/dev.132142","type":"journal-article","created":{"date-parts":[[2016,10,22]],"date-time":"2016-10-22T00:58:00Z","timestamp":1477097880000},"page":"4462-4473","source":"Crossref","is-referenced-by-count":29,"title":["Six3 dosage mediates the pathogenesis of holoprosencephaly"],"prefix":"10.1242","volume":"143","author":[{"given":"Xin","family":"Geng","sequence":"first","affiliation":[{"name":"Oklahoma Medical Research Foundation 1 , Oklahoma City, OK 73104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Acosta","sequence":"additional","affiliation":[{"name":"Center for Vascular and Developmental Biology, Feinberg Cardiovascular Research Institute, Northwestern University 2 , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Lagutin","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital 3 Department of Genetics , , Memphis, TN 38105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyea Jin","family":"Gil","sequence":"additional","affiliation":[{"name":"Center for Vascular and Developmental Biology, Feinberg Cardiovascular Research Institute, Northwestern University 2 , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3984-7615","authenticated-orcid":false,"given":"Guillermo","family":"Oliver","sequence":"additional","affiliation":[{"name":"Center for Vascular and Developmental Biology, Feinberg Cardiovascular Research Institute, Northwestern University 2 , Chicago, IL 60611 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061213211079100_DEV132142C1","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1242\/dev.101790","article-title":"The facial neural crest controls fore- and midbrain patterning by regulating Foxg1 expression through Smad1 activity","volume":"141","author":"Aguiar","year":"2014","journal-title":"Development"},{"key":"2024061213211079100_DEV132142C2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1242\/dev.067660","article-title":"Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning","volume":"139","author":"Beccari","year":"2012","journal-title":"Development"},{"key":"2024061213211079100_DEV132142C3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1242\/dmm.018275","article-title":"Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice","volume":"8","author":"Billington","year":"2015","journal-title":"Dis. 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