Organism and organ size control
The control of organ (or organism) size is a fundamental aspect of life ? What makes an elephant grow a million times larger than a mouse? How do our two hands develop independently of each other yet reach very similar size? How does a liver precisely regenerate its original mass when two-thirds of it is removed? The coordination of cell proliferation and cell death is essential for proper organ size during development and for maintaining tissue homeostasis throughout postnatal life
The recent discovery of a novel signaling network in Drosophila, known as the Hippo (Hpo) pathway, might provide an important entry point to these fascinating questions. The Hpo pathway consists of several negative growth regulators acting in a kinase cascade that ultimately phosphorylates and inactivates Yorkie (Yki), a transcriptional coactivator that positively regulates cell growth, survival, and proliferation. Components of the Hpo pathway are highly conserved throughout evolution, suggesting that this pathway may function as a global regulator of tissue homeostasis in all metazoan animals. (Pan D ( 2007) Genes Devel. Hippo signalling in organ size control. vol 21, : 886-97)
In Drosophila, cell proliferation and cell death are orchestrated by the Hippo kinase cascade, a growth-suppressive pathway that ultimately antagonizes the transcriptional coactivator Yorkie (Yki). A single phosphorylation site in Yki mediates the growth-suppressive output of the Hippo pathway. Hippo-mediated phosphoryiation inactivates Yki by excluding it from the nucleus, whereas loss of Hippo signaling leads to nuclear accumulation and therefore increased Yki activity. A mammalian Hippo signaling pathway also culminates in the phosphorylation of YAP, the mammalian homolog of Yki. The mammalian Hippo pathway is a potent regulator of organ size, and that its dysregulation leads to tumorigenesis. ( Dong J ( 2007,) Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell, 130, 1120-33 )
Which is part of the explanation for why a mouse and an elephant are somewhat different in size.
As an aside it is fascinating how such complex and far reaching are controlled by phosphorylation, acetylation and methylation.
- Martin Eastwood