牙颌面骨畸形机制研究的现状与发展
江凌勇

Status and advances in the mechanism research on dento-maxillofacial skeletal abnormalities
JIANG Lingyong
表1 条件性基因编辑小鼠鉴定得到的牙颌面关键细胞谱系及其相关畸形致病基因
Tab 1 Key cell lineages and related genes responsible for dento-maxillofacial abnormalities through conditional gene-edited mice
Key cell lineage (marker-Cre)GenePathwayCharacteristic of abnormalitiesRelated phenotype, syndrome or diseaseReference
NCC (Wnt1-Cre)Med23WNT signaling③④Pierre Robin syndrome, micrognathia, cleft palate[35]
NCC (Wnt1-Cre)Fgf18WNT signaling①③④Micrognathia, cleft palate, hypoplastic craniofacial bones[36]
NCC (Wnt1-Cre)Six1WNT signaling, BMP signaling③④Branchio-oto-renal syndrome, micrognathia, cleft palate with ankyloglossia[37]
NCC (Wnt1-Cre)Bmp2BMP signaling③④Pierre Robin syndrome[38]
NCC (Wnt1-Cre)Bmp4BMP signaling②③④Severe deformation of molar buds, palate, and maxilla-mandibular bony structures; defected Meckel's cartilage[32]
NCC (Wnt1-Cre)Foxf2SHH signaling④Cleft palate[39]
NCC (Wnt1-Cre)Setdb1BMP signaling, WNT signaling④Cleft palate[40]
NCC (Wnt1-Cre)Ift20WNT signaling①③④Death shortly after birth due to difficulties in feeding and breathing, severe craniofacial malformation, loss of craniofacial bones, frontonasal dysplasia, micrognathia, cleft palate[41-42]
NCC (Wnt1-Cre, Sox9-Cre)G9aSHH signalingWnt1: ①③; Sox9: ①②

Wnt1: death shortly after birth, shortened maxilla, restricted airway, frontonasal dysplasia

Sox9: death shortly after birth, cranial skeletal dysplasia, smaller tooth germ, impaired tooth inner enamel epithelium

[43-45]
NCC (Wnt1-Cre)Tak1FGF signaling③④Pierre Robin syndrome, micrognathia, abnormal tongue, cleft palate[46]
NCC (Wnt1-Cre)Tgfbr2FGF signaling‒Abnormal tongue[47]
NCC (Wnt1-Cre)Nell1WNT signaling①Craniosynostosis[48]
NCC (Wnt1-Cre)Dlx3WNT signaling①③Tricho-dento-osseous syndrome, defected frontal bone and mandible[49]
NCC (Wnt1-Cre)Yap/TazWNT signaling①③Neural tube malformation, craniofacial vascular malformation, mandibular abnormalities[50]
NCC (Wnt1-Cre)Tfap2

WNT signaling,

RA signaling

①③④Branchio-oto-renal syndrome, midface cleft, defected craniofacial bone[51]
NCC (Wnt1-Cre)Twist1FGF signaling①Defected craniofacial bone[52]
NCC (Wnt1-Cre)Brca1/2P53 signaling①④Craniostenosis, cleft palate, defected craniofacial bone[53]
NCC (Wnt1-Cre)SmoSHH signaling①Defected craniofacial bone[54]
NCC (Wnt1-Cre)Ldb1WNT signaling④Cleft palate[55]
NCC (Wnt1-Cre)OsxFGF signaling①③Micrognathia, defected craniofacial bone[28]
First branchial arch mesenchymal cell (Pax2-Cre)Bmp4BMP signaling‒Bilateral hyperplastic tissues[32]
First branchial arch mesenchymal cell (Hand2-Cre)Twist1FGF signaling③④Micrognathia, cleft palate[56]
Mesenchymal cell (Twist2-Cre)Fgf18WNT signaling①③Micrognathia, defected craniofacial bone[36]
Mesenchymal cell (Twist1-Cre)Twist1FGF signaling②Defected dentin and enamel, tooth abnormalities[57]
Osteoblast (Prx1-Cre)Ift20WNT signaling①Craniostenosis[58]
Osteoblast (Osx-Cre, Col1-Cre)Fgfr3WNT signaling①

Osx: CATSHL syndrome, frontonasal dysplasia

Col1: CATSHL syndrome

[59-60]
Osteoblast (Osx-Cre)RarRA signaling①③Vitamin A deficiency, micrognathia, frontonasal dysplasia[61]
Osteoblast (Prx1-Cre, Osx-Cre)Ror2BMP signaling, STAT signaling①②③Robinow syndrome, brachyrhinia[62]
Osteoblast (Prx1-Cre, Osx-Cre)Stat3STAT signaling①③AD-HIES syndrome, defected craniofacial bone[3,63]
Osteoblast/chondroblast (Dermo1-Cre, Col2a1-Cre, Prx1-Cre, Osx-Cre)CbfbWNT signaling①②③

Dermo1 & Col2a1: Cleidocranial dysostosis, hypomineralized craniofacial bones, clavicle dysplasia

Prx1: Cleidocranial dysostosis, hypomineralized parietal bones, clavicle missing

Osx: Cleidocranial dysostosis, hypomineralized parietal bones, tooth deformities

[30,64-65]
Osteoblast/chondroblast (Prx1-Cre, Col2-Cre)Recql4P53 signaling①②Rothmund-Thomson syndrome, Baller-Gerold syndrome[66]
Chondroblast (Col2-Cre)Yap/TazWNT signaling①④Defected craniofacial bone, cleft palate[67]
Osteoblast (Ocn-Cre)WlsWNT signaling①③Defected craniofacial bone, molar deformity[68]
Osteoblast (Ocn-Cre)Ift20WNT signaling①Osteopenia-like phenotypes in skulls[42]
Osteoblast (Osx-Cre)Notch2Notch signaling①②③Hajdu-Cheney syndrome[69-70]
Osteoblast (Osx-Cre)Fgfr2FGF signaling①②③Crouzon syndrome[71-72]
Osteoblast (Prrx1-Cre)GαRANKL signaling①Fibrous dysplasia[73]
Osteoblast (Osx-Cre)Efnb1Unclear①③Larger cranial height, larger interorbital and nasal widths, smaller maxillary width[74]
Osteoblast (Osx-Cre)Atg5MMP signaling①Defected craniofacial bone[75]
Osteoblast (Osx-Cre)Fip200MMP signaling①Defected craniofacial bone[75]
Epithelial cell (Krt14-Cre、Eiia-Cre)Wnt10aWNT signaling②Taurodontism[76]
Epithelial cell (Krt14-Cre)Tgfbr2WNT signaling④Soft palate cleft[77]
Epithelial cell (Krt14-Cre)Dlx3WNT signaling②Hypomineralized enamel[78]
Epithelial cell (Krt14-Cre)Fgfr2FGF signaling②Retarded tooth formation, cleft palate[79]
Epithelial cell (Shh-Cre)WlsWNT signaling②Defective ameloblast and odontoblast differentiation[76]
CNC-derived cell subset in the developing palatal mesenchyme (Osr2-Cre)β-cateninWNT signaling④Cleft palate[80]
CNC-derived cell subset in the developing palatal mesenchyme (Osr2-Cre)Runx2RA signaling④Cleft palate[33]
Pharyngeal endoderm cell (Foxg1-Cre)Tbx1Unclear①③Velo-cardio-facial syndrome[81]