Effect Of FGF10/FGFR2b Signaling Pathway On Mouse Pancreas Development

The pancreas is considered as one of the important organs of the human body.It controls the body's metabolism.Besides,the normal growth and development of the pancreas is the foundation to ensure the orderly progress of life activities.Based on the morphological evolution process of mouse embryonic pancreas,it can be divided into three stages,that is,the embryonic period E8.5-E12.5.When the pancreas begins to sprout,a large number of transcription factors and growth factors,including Pdx1,P48,Sox9,FGF10 are expressed in the pancreatic bud in order to coordinate and control the proliferation and differentiation of pancreatic progenitor cells.E12.5-E16.5 is the second transitional stage of pancreatic development.At this time,pancreatic-specific genes proliferate rapidly with the aim to form a pool of progenitor cells.Subsequently,the cell proliferation capacity gradually decreases and the pancreas morphology changes.E16.5-post-birth is the third transitional period.After E16.5,the morphology and function of the embryo's acinar,duct,and islets present the tendency to mature.During the development of the mouse pancreas,FGF10,FGFR2b and pancreatic transcription factors coordinate the control of proliferation and differentiation of progenitor cells,which provides great guidance on the direction of their differentiation,and their accurate expression exerts an impact on the morphological evolution of acinar,ducts and islets.Functional maturity generates a certain regulatory effect.Previously,it could be found that FGF10^-/-mice were fatal at birth,and FGF10^+/-mice had abnormal blood glucose levels.In the meanwhile,they also showed a significant decrease in insulin-expressing cells,indicating that FGF10 has a regulatory effect on pancreatic islet function.However,the specific stage where FGF10 affects pancreatic development in this process remains unclear.Therefore,we first used the r Tt A(Tet O)s Fgfr2b mouse model to explore the current problem.It was induced by injection of doxycycline from E9.5 and E10.5 to E13.5.Observation of E14.5 demonstrated that the pancreas of mice in the experimental group was small and the differentiation of progenitor cells was delayed.According to the observation of E18.5 showed that the central cavity of the pancreas is larger in diameter and rosettes are arranged irregularly with less insulin secretion.However,it was induced from E12.5 to E13.5,E14.5 that the pancreas of mice remained more normal.In addition,it was induced from E12.5 to E14.5,E14.5 to E17.5,E18.5,that the pancreas of mice also remained normal.As a result,our results indicate that during mouse pancreas development,FGFR2b mainly regulates the differentiation of pancreatic progenitor cells at E9.5 and E10.5.Moreover,this damage cannot be self-repaired and will follow until later stages of the development.Subsequently,we bred Prx1-Cre;FGF10^fl/fl mice with FGF10^fl/fl mice,and obtained materials on E16.5 days and E18.5 days respectively,finding that FGF10^-/-mice were similar to the previous results.Therefore,the results at this time indicate that the FGF10/FGFR2b signaling pathway exerts a major role in the early development of the pancreas.