Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much more.More specifically,recent research has demonstrated the importance of...Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much more.More specifically,recent research has demonstrated the importance of Notch signaling in osteogenic differentiation,bone healing,and in the development of the skeleton.The craniofacial skeleton is complex and understanding its development has remained an important focus in biology.In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton,skull,and face develop.We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system,and what importance it may play in the future.展开更多
During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial struc...During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.展开更多
Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although th...Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.展开更多
基金the National Institutes of Health(CA226303to TCH)the U.S.Department of Defense(OR130096 to JMW)+5 种基金the Scoliosis Research Society(TCH and MJL)the Pritzker-Northshore Fellowship at The University of Chicagothe Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund。
文摘Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much more.More specifically,recent research has demonstrated the importance of Notch signaling in osteogenic differentiation,bone healing,and in the development of the skeleton.The craniofacial skeleton is complex and understanding its development has remained an important focus in biology.In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton,skull,and face develop.We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system,and what importance it may play in the future.
基金supported by the National Natural Science Foundation of China(82071096 to X.W,31970585,32170544,and 31801056 to Q.B.)the National Key Research and Development Program of China(2017YFC1001800 to X.W.,2018YFC1004703 to Q.B),the Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(JYZZ179 to J.S.)+1 种基金the Innovative research team of high-level local universities in Shanghai(SHSMU-ZLCX20211700)the SHIPM-pi fund No.JY201803 from Shanghai Institute of Precision Medicine,Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.
文摘During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.
基金supported by the National Natural Science Foundation of China(No.82271889,82572117,82371173,82172105)the National Key Research and Development Program of China(No.2021YFC2701000)Shanghai Natural Science Foundation(23ZR1409400,24ZR1409400)。
文摘Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.
