Gli2 and Gli3 synergistically mediate HH-TGF-βcrosstalk in mesenchymal progenitor cells to orchestrate tooth root morphogenesisOA
Hedgehog(HH)signaling is essential in directing the fate determination of postmigratory cranial neural crest cells(CNCCs)to ensure proper craniofacial development.Gli transcription factors(TFs)are established as primary effectors of HH signaling,yet their distinct roles and regulatory mechanisms in governing cell commitment and differentiation of postmigratory CNCCs remain poorly understood.Here,using tooth root as a model,we combined transgenic mouse models with bioinformatic analyses to interrogate the functions of Gli2 and Gli3 in CNCC-derived root progenitor cells of the mouse molar.We revealed that loss of Gli3 alone in dental mesenchymal root progenitor cells caused shortened roots and that concurrent loss of Gli2 and Gli3 exacerbated root malformations,concomitant with profound impairments in cell proliferation and multilineage differentiation,suggesting a synergistic interaction between Gli2 and Gli3 during tooth root development.Mechanistically,Gli2 and Gli3 cooperatively regulated the transcription of Acvr2b,thereby modulating the activity of TGF-β/SMAD signaling within the dental mesenchyme.This Gli2/Gli3-TGF-βsignaling cascade was critical for the lineage specification of tooth root progenitor cells during molar morphogenesis.Collectively,this work uncovers synergistic interactions of Gli2 and Gli3 in orchestrating tooth root morphogenesis and provides a novel insight into HH-TGF-βcrosstalk in cell fate decisions of postmigratory CNCCs.
Tao Zhou;Linyang Huang;Yaxin Xie;Yijia Yin;Yufei Yao;Li Mei;Paul RCooper;Hu Zhao;Xianglong Han;Junjun Jing
State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaFaculty of Dentistry,University of Otago,Dunedin,New ZealandFaculty of Dentistry,University of Otago,Dunedin,New ZealandChinese Institute for Brain Research,Beijing,ChinaState Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,ChinaState Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,China
医药卫生
bioinformatic analysessynergistic interactiontooth rootcraniofacial developmentgli transcription factors tfsfate determinationneural crest cells cnccsglitransgenic mouse models
《International Journal of Oral Science》 2026 (3)
P.416-427,12
the support from the National Natural Science Foundations of China(U24A20712,82271022,and 82370915)National Key R&D Program of China(2024YFC2510700)Innovative Research Group of the National Natural Science Foundation of Sichuan Province(2025NSFTD0026)。
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