The Hippo Pathway

Abstract

In multicellular organisms control over organ size and shape is of utter importance. However, the regulation of control is rather complex. An involved signalling route is the Hippo pathway. In this review, the core cascade and downstream target of the Hippo pathway will be discussed. The first components of the pathway, Warts, Salvador, Hippo and Mats, were discovered in a search for tumour suppressors in the fruitfly (Drosophila melanogaster). The downstream target is the transcription co-activator Yorkie (YKI), which targets many genes implicated in proliferation and apoptosis. These processes are involved in growth control. Deregulation can, therefore, result in severe effects, such as tumourigenesis. Furthermore, the upstream regulators of the Hippo pathway will be disclosed. Various factors are shown to regulate the Hippo pathway core kinases and/or Yorkie. The vastness of the upstream regulators is required for tissue, timing and organism specificity. In order for the Hippo pathway to affect the overall tissue, communication between cells is necessary. Therefore, cell-cell interactions are required to tightly control and modulate Hippo activity between neighbouring cells. Cross talk between the Hippo pathway and other mechanisms is necessary to coordinate the complex development and homeostasis of tissue size, shape and patterning. Taken together, the Hippo pathway is important for processes, such as proliferation and apoptosis. Even though, the regulation of the pathway is understood more and more, research is required to elucidate the signalling route even further. Since deregulation of the pathway can result in tumour formations, better understanding of the pathway could help better understand tumour development and progression. Moreover, insights in the signalling route might help develop therapeutic targets for cancer and other diseases.