{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:10:21Z","timestamp":1792275021750,"version":"4.4.0"},"reference-count":35,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":3425,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title><jats:p>Bone morphogenetic protein (BMP) receptor type 1A (BMPR1A) mutations are associated with facial dysmorphism, which is one of the main clinical signs in both juvenile polyposis and chromosome 10q23 deletion syndromes. Craniofacial development requires reciprocal epithelial\/neural crest (NC)-derived mesenchymal interactions mediated by signaling factors, such as Bmp, in both cell populations. To address the role of mesenchymal Bmp signaling in craniofacial development, we generated a conditional knockdown mouse by expressing the dominant-negative Bmpr1a in NC-derived cells expressing the Myelin protein zero (Mpz)-Cre transgene. At birth, 100% of the conditional mutant mice had wide-open anterior fontanelles, and 80% of them died because of cleft face and cleft palate soon after birth. The other 20% survived and developed short faces, hypertelorism, and calvarial foramina. Analysis of the NC-derived craniofacial mesenchyme of mutant embryos revealed an activation of P53 apoptosis pathway, and down-regulation of both c-Myc and Bcl-XL; a normal growth rate but an incomplete expansion of mesenchymal cells. These findings provide genetic evidence indicating that optimal Bmpr1a-mediated signaling is essential for NC-derived mesenchymal cell survival in both normal nasal and frontal bone development and suggest that our model is useful for studying some aspects of the molecular etiology of human craniofacial dysmorphism.<\/jats:p>","DOI":"10.1242\/dmm.009274","type":"journal-article","created":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T06:31:15Z","timestamp":1341556275000},"source":"Crossref","is-referenced-by-count":29,"title":["Facial dysmorphism induced by bone morphogenetic protein receptor type 1A-mediated signaling reduction in neural crest-derived cells"],"prefix":"10.1242","author":[{"given":"Hiromitsu","family":"Saito","sequence":"first","affiliation":[{"name":"Mie University Life Science Research Center, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Kumamoto University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Mie University Life Science Research Center, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2021042501054649900_b1-0050948","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-2184.2008.00576.x","article-title":"Myc down-regulation affects cyclin D1\/cdk4 activity and induces apoptosis via Smac\/Diablo pathway in an astrocytoma cell line","volume":"42","author":"Amendola","year":"2009","journal-title":"Cell Prolif."},{"key":"2021042501054649900_b2-0050948","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1182\/blood.V82.7.2079.2079","article-title":"Activation of apoptosis associated with enforced myc expression in myeloid progenitor cells is dominant to the suppression of apoptosis by interleukin-3 or erythropoietin","volume":"82","author":"Askew","year":"1993","journal-title":"Blood"},{"key":"2021042501054649900_b3-0050948","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1101\/gad.1202604","article-title":"In vivo convergence of BMP and MAPK signaling pathways: impact of differential Smad1 phosphorylation on development and homeostasis","volume":"18","author":"Aubin","year":"2004","journal-title":"Genes Dev."},{"key":"2021042501054649900_b4-0050948","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1242\/dev.128.20.3975","article-title":"Severe nasal clefting and abnormal embryonic apoptosis in Alx3\/Alx4 double mutant mice","volume":"128","author":"Beverdam","year":"2001","journal-title":"Development"},{"key":"2021042501054649900_b5-0050948","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1002\/dvdy.20833","article-title":"Recent advances in craniofacial morphogenesis","volume":"235","author":"Chai","year":"2006","journal-title":"Dev. 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