The cochlear auditory epithelium contains two types of sound receptors,inner hair cells(IHCs)and outer hair cells(OHCs).Mouse models for labelling juvenile and adult IHCs or OHCs exist;however,labelling for embryonic ...The cochlear auditory epithelium contains two types of sound receptors,inner hair cells(IHCs)and outer hair cells(OHCs).Mouse models for labelling juvenile and adult IHCs or OHCs exist;however,labelling for embryonic and perinatal IHCs or OHCs are lacking.Here,we generated a new knock-in Fgf8^(P2A-3×GFP/+)(Fgf8^(GFP)/+)strain,in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements.After confirming that GFP expression accurately reflects the expression of Fgf8,we successfully obtained both embryonic and neonatal IHCs with high purity,highlighting the power of Fgf8^(GFP)/+.Furthermore,our fate-mapping analysis revealed,unexpectedly,that IHCs are also derived from inner ear progenitors expressing Insm1,which is currently regarded as an OHC marker.Thus,besides serving as a highly favorable tool for sorting early IHCs,Fgf8^(GFP)/+will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.展开更多
The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control since their teeth share highly conserved and well-characterized developmental pro...The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control since their teeth share highly conserved and well-characterized developmental processes, and their developmental tempo varies notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrated that the dental mesenchyme dominates the tooth developmental tempo and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3 K-Akt intracellular signaling,and impelled the transition of the cell cycle from G1-to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo, and the dental mesenchymal FGF8 could be a pivotal factor in controlling the developmental pace in a non-cell-autonomous manner during mammalian odontogenesis.展开更多
基金funded by the National Key R&D Program of China(2021YFA1101804)the Strategic Priority Research Program of the Chinese Academy of Science(XDB32060100)+3 种基金the National Natural Science Foundation of China(91949119,82101212,and 82101209)a Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Science and Technology Commission of Shanghai Municipality(21ZR1440200)the Shanghai Sailing Program(20YF1426400).
文摘The cochlear auditory epithelium contains two types of sound receptors,inner hair cells(IHCs)and outer hair cells(OHCs).Mouse models for labelling juvenile and adult IHCs or OHCs exist;however,labelling for embryonic and perinatal IHCs or OHCs are lacking.Here,we generated a new knock-in Fgf8^(P2A-3×GFP/+)(Fgf8^(GFP)/+)strain,in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements.After confirming that GFP expression accurately reflects the expression of Fgf8,we successfully obtained both embryonic and neonatal IHCs with high purity,highlighting the power of Fgf8^(GFP)/+.Furthermore,our fate-mapping analysis revealed,unexpectedly,that IHCs are also derived from inner ear progenitors expressing Insm1,which is currently regarded as an OHC marker.Thus,besides serving as a highly favorable tool for sorting early IHCs,Fgf8^(GFP)/+will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.
基金supported by the National Natural Science Foundation of China (81870739, 82001002, 81271102, 81771034)the Natural Science Foundation of Fujian Province (2019J01281, 2020J01180)。
文摘The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control since their teeth share highly conserved and well-characterized developmental processes, and their developmental tempo varies notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrated that the dental mesenchyme dominates the tooth developmental tempo and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3 K-Akt intracellular signaling,and impelled the transition of the cell cycle from G1-to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo, and the dental mesenchymal FGF8 could be a pivotal factor in controlling the developmental pace in a non-cell-autonomous manner during mammalian odontogenesis.
