In Drosophila, there is a single EGF receptor with multiple EGF ligands, and EGF signaling has been implicated in embryonic pattern formation, larval disc proliferation, and multiple cell fate decisions [ 10- 12].
This might be advantageous for enabling a population of cells to make multiple cell fate decisions.
Genetic evidence indicates that the tumor suppressors Ink4a/Arf and Trp53 regulate multiple HSC fate decisions (Akala et al., 2008; Liu et al., 2009; Oguro et al., 2006).
Members of the transforming growth factor-beta (TGF β) growth factors are pleiotropic cytokines that govern multiple cell fate decisions during development, differentiation and tissue homeostasis.
Multiple studies have demonstrated that cell fate decisions are determined not only by activation of certain signalling pathways, but also depend on the spatiotemporal dynamics, including signal duration and strength.
Mechanistically, ERK5 was proposed to act independently to maintain naive pluripotency and control cell fate decisions in mouse embryonic stem cells, suggesting multiple critical functions for this kinase during differentiation30.
Multiple extrinsic and intrinsic factors regulate RPC proliferation and cell fate decisions during development (Livesey and Cepko 2001; Martins and Pearson 2008).
Both approaches reveal the presence of multiple specific reactions involved in the distinct dynamics of ERK responses and the cell fate decisions they trigger.
In contrast to a prior emphasis on the finality of cell fate decisions in developmental systems, cellular plasticity is now emerging as a general theme in the biology of multiple adult organ systems.
Thus, not just for the organ size control, the Hippo pathway receives inputs from multiple extracellular or intracellular signals and interacts with other essential signaling pathways to play critical roles in many aspects for cell fate decisions.
