Low-expressed Kuzbanian In Drosophila Stomach Limits The Activation Of Notch Signaling To Maintain Gastric Epithelial Homeostasis

The gastrointestinal tract has recently come to the forefront of multiple research fields.It is now recognized as a major source of signals modulating food intake,insulin secretion and energy balance.Homeostatic control of gastrointestinal epithelial tissue is also our focus.multipotent gastric stem cells(GSSCs)in the copper cell region of adult Drosophila midgut can produce all epithelial cell lineages found in the region,including acid-secreting copper cells,interstitial cells and enteroendocrine cells,but mechanisms controlling their quiescence and the fate of their daughter cell are unknown.By using Immunostaining,we demonstrate that activation of the Notch signaling pathway does occur in CCR,and the GSSCs have expressed Delta.By overexpressing several Notch isoforms with different lengths of extracellular domains in stem cells,different degrees of Notch activation in CCR prove that when Notch isoforms contain S2 cleavage sites,the degree of Notch activation in CCR will be limited.RT-q PCR results indicate that this is because kuz is less expressed in CCR than other regions.By using genetic analysis,we rescue this phenotype when kuz is overexpressed,but it leads to all stem cells are lost in CCR.Overexpression of the JAK / STAT signaling pathway causes the same phenotype.The results of damageinduced regeneration assays combined with cell lineage tracing show that this loss may be related to ee cells expressing esg and DL in CCR,or GSSCs and GBs will activate the Notch signal path to each other.In summary,we show that kuzbanian is a direct factor that limits the activation of Notch in CCR,and the expression of kuz may be controlled by the JAK / STAT pathway in the intestine,which results in a low level of kuz expression in CCR.The mechanism of GSSCs differentiation to their daughter cells in CCR may be related to kuz,but it needs further experiments to prove.