title: Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells.
abstract: Neural crest (NC) cells are a group of cells located in the neural folds at the boundary between the neural and epidermal ectoderm. Cranial NC cells migrate to the branchial arches and give rise to the majority of the craniofacial region, whereas trunk and tail NC cells contribute to the heart, enteric ganglia of the gut, melanocytes, sympathetic ganglia, and adrenal chromaffin cells. Positional information is indispensable for the regulation of cranial or trunk and tail NC cells. However, the mechanisms underlying the regulation of positional information during human NC induction have yet to be fully elucidated. In the present study, supplementation of bone morphogenetic protein (BMP) 4 in defined serum-free culture conditions including fibroblast growth factor-2 and Wnt3a from day 8 after NC specification induced the expression of cranial NC markers, AP2alpha, MSX1, and DLX1, during NC cell differentiation from human pluripotent stem cells. On the other hand, the proportion of cells expressing p75(NTR) or HNK1 decreased compared with that of cells cultured without BMP4, whereas gene expression analysis demonstrated that the expression levels of cranial NC-associated genes increased in BMP4-treated NC cells. These BMP4-treated NC cells were capable of differentiation into osteocytes and chondrocytes. The results of the present study indicate that BMP4 regulates cranial positioning during NC development.
authors.affiliation: Laboratory of Stem Cell Cultures, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Mimura
authors.forename: Mika
authors.initials: M
authors.lastname: Suga
authors.forename: Kaori
authors.initials: K
authors.lastname: Okada
authors.forename: Masaki
authors.initials: M
authors.lastname: Kinehara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nikawa
authors.forename: Miho K
authors.initials: MK
authors.lastname: Furue
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D005147:Facial Bones / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects* / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D055415:Bone Morphogenetic Protein 4; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors