Developmental morphogens and adult liver repair
Hedgehog and Notch are among the morphogenic signaling pathways that are typically inactivated once liver development finishes. Both pathways reactivate in adulthood in response to liver injury so that healthy liver tissue can be regenerated. Because these pathways have pleiotropic actions that control cell fate, they are tightly regulated. Dysfunction of the regulatory mechanisms can lead to either insufficient, or excessive, pathway activity - both result in progressive liver damage. The adult liver is designed to resist injury. Notch is crucial during liver development because it coordinates biliary differentiation and morphogenesis of intrahepatic and extrahepatic bile ducts, as well as the gallbladder. The effect of the Notch pathway in liver carcinogenesis is diverse and receptor-dependent. There is growing evidence that Notch signaling reconfigures cellular metabolic pathways, with consequences for the metabolic syndrome, as well as cancer biology. The effect of Notchon adipocyte metabolism/function seems to be vary according to the receptor.
