{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:48:26Z","timestamp":1790837306001,"version":"4.1.0"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE027662 R01DE020843"],"award-info":[{"award-number":["R01DE027662 R01DE020843"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Cranial neural crest cells (NCCs) are the origin of the anterior part of the face and the head. Cranial NCCs are multipotent cells giving rise to bones, cartilage, adipose-tissues in the face, and neural cells, melanocytes, and others. The behavior of cranial NCCs (proliferation, cell death, migration, differentiation, and cell fate specification) are well regulated by several signaling pathways; abnormalities in their behavior are often reported as causative reasons for craniofacial anomalies (CFAs), which occur in 1 in 100 newborns in the United States. Understanding the pathological mechanisms of CFAs would facilitate strategies for identifying, preventing, and treating CFAs. Bone morphogenetic protein (BMP) signaling plays a pleiotropic role in many cellular processes during embryonic development. We and others have reported that abnormalities in BMP signaling in cranial NCCs develop CFAs in mice. Abnormal levels of BMP signaling cause miscorrelation with other signaling pathways such as Wnt signaling and FGF signaling, which mutations in the signaling pathways are known to develop CFAs in mice and humans. Recent Genome-Wide Association Studies and exome sequencing demonstrated that some patients with CFAs presented single nucleotide polymorphisms (SNPs), missense mutations, and duplication of genes related to BMP signaling activities, suggesting that defects in abnormal BMP signaling in human embryos develop CFAs. There are still a few cases of BMP-related patients with CFAs. One speculation is that human embryos with mutations in coding regions of BMP-related genes undergo embryonic lethality before developing the craniofacial region as well as mice development; however, no reports are available that show embryonic lethality caused by BMP mutations in humans. In this review, we will summarize the recent advances in the understanding of BMP signaling during craniofacial development in mice and describe how we can translate the knowledge from the transgenic mice to CFAs in humans.<\/jats:p>","DOI":"10.3389\/fphys.2023.1170511","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T01:02:46Z","timestamp":1684371766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["BMP signaling during craniofacial development: new insights into pathological mechanisms leading to craniofacial anomalies"],"prefix":"10.3389","volume":"14","author":[{"given":"Hiroki","family":"Ueharu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Mishina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.bone.2017.06.011","article-title":"The obligatory role of Activin A in the formation of heterotopic bone in Fibrodysplasia Ossificans Progressiva","volume":"109","author":"Alessi Wolken","year":"2018","journal-title":"Bone"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e23034","DOI":"10.1002\/dvg.23034","article-title":"Specific and spatial labeling of P0-Cre versus Wnt1-Cre in cranial neural crest in early mouse embryos","volume":"55","author":"Chen","year":"2017","journal-title":"Genesis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00441-018-2944-5","article-title":"Conditional deletion of Bmp2 in cranial neural crest cells recapitulates Pierre Robin sequence in mice","volume":"376","author":"Chen","year":"2019","journal-title":"Cell. 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