A similar, general effect is observed on loss-of-function mutations of the other core kinase cascade members. The Hippo gene ( Hpo) was named due to the highly proliferative overgrowth phenotype upon loss-of-function mutation of the Hpo gene and consequently observed increased head size in the Drosophila this phenotype somewhat resembled a Hippo head under the microscope. Moreover, just homozygous loss of Yap results in extreme morphological disruption in mouse embryos and an inability to survive beyond embryonic day 10.5. In such cases, embryos fail to progress past morula stage, likely due to the role both gene products play in lineage specification during embryogenesis. This role is evidenced by the early embryonic lethality observed when the primary, downstream transcriptional activators of the pathway, Yap (encoded by Yap1) and Taz (encoded by Wwtr1), are both lost in mice. Genes identified include Warts ( Wts, LATS1/2 in human) and Hippo ( Hpo, or STK4/3 encoding MST1/2 in human), which encode the kinases that constitute the phosphorylation cascade central to the Hippo pathway, which is a central regulator of early stage development in embryogenesis.

The pathway was initially discovered in Drosophila melanogaster following identification of core genes regulating organ size control and cellular overgrowth via mosaic screening. The Hippo pathway is an evolutionarily conserved signalling cascade regulated by a broad spectrum of upstream effectors and acts as an integral mechanosensory component of cells, transducing physical signals at the plasma membrane and regulating response via control of differentiation and proliferation in cells.

Sims 4 traits cancer mod