text: An individual signal transduction pathway can regulate several proteins (e.g. kinases) as well as the activation of many genes. The consequences to the properties of the cell can be, therefore, very prominent. Identifying these properties (through theoretical predictions and experimentation) sheds light on the function of the pathway and provides possible new therapeutic targets.
  Activation of the notch/STAT3-Ser/Hes3 signaling axis has significant consequences to several cell types; effects have been documented both in vitro and in vivo:
  :* Cultured fetal and adult rodent neural stem cells: Pro-survival effects; increased yield; increased expression of sonic hedgehog protein.
  :* In vivo adult rodent neural stem cells: Increase in cell number; increased expression of Sonic hedgehog (Shh) protein. Delta4 administration in the adult rodent brain has also been shown to augment the effect of basic fibroblast growth factor and epidermal growth factor in promoting the proliferation of neural precursor cells in the subventricular zone and hypothalamus following ischemic stroke.
  :* Cultured adult monkey neural stem cells: Pro-survival effects; increased yield; increased expression of sonic hedgehog protein.
  :* Cultured putative glioblastoma multiforme cancer stem cells: Pro-survival effects (Hes3 knockdown by RNA interference reduces cell number).
  :* Cultured bovine chromaffin progenitor cells: Several activators of the signaling pathway increase cell yield.
  :* Cultured mouse insulinoma cells (MIN6 cell line): These cells can be cultured efficiently under conditions that promote the operation of the signaling pathway; Hes3 RNA interference opposes growth and the release of insulin following standard protocols that evoke insulin release from these cells.
  :* Mice that are engineered to lack the Hes3 gene exhibit increased sensitivity to treatments that damage endocrine pancreas cells.
  :* Recent research implicates Hes3 in direct reprogramming of adult mouse cells to the neural stem cell state; a causative relation remains to be determined.
  :* Hes3 and components of the Signaling Axis are regulated during critical stages of reprogramming (Mouse Embryonic Fibroblast - to - Embryonic Stem Cell reprogramming).
  :* Mice genetically engineered to lack the Hes3 gene fail to upregulate the transcription factor Neurogenin3 during pancreatic regeneration (induced by streptozotocin treatment). This is indicative of a compromised regenerative response.