Figure 7. Model illustrating the relative influence of EGFR/Ras/Raf/MAPK and InR/Pi3K/TOR signalling on ISC proliferation and EB/EC endoreplication.

Upper panel: Under normal physiological conditions, both EGFR/MAPK and InR/Pi3K/TOR pathways act in progenitor cells to control their proliferation and growth. But only the InR/Pi3K/TOR pathway, and not the EGFR/MAPK pathway, is active in ECs to promote their growth with endoreplication. Lower panel: During infection-induced regeneration, EGFR/MAPK signaling is strongly induced in progenitor cells and inherited by their progeny. This results in hyperproliferation of ISCs and hypertrophy and higher ploidy in ECs. EGFR/MAPK signaling post-transcriptionally up-regulates E2f1 to induce this EC endorelplication.