**2.5 Interplay between insulin pathway and ecdysone determines final body size**

Taken together the above findings suggest that the insulin-signalling pathway acts in the prothoracic gland (PG) to regulate the release of ecdysone and determine the length of the larval growth period (Caldwell, Walkiewicz, and Stern 2005; Colombani et al. 2005; King-Jones et al. 2005; Mirth, Truman, and Riddiford 2005; Shingleton 2005; Prober and Edgar 2002). For instance, increased PG growth occurs when PI3-kinase (PI3K, a downstream regulator of the insulin pathway) is upregulated in the PG (Caldwell, Walkiewicz, and Stern 2005; Mirth, Truman, and Riddiford 2005). The PG overgrowth causes accelerated metamorphosis, which results in reduced adult size due to the rapid progression through the larval growth stage. Precocious ecdysone release, as measured by premature increase in levels of the early response ecdysone genes, correlates with this disruption to larval growth. Conversely, reducing growth of the PG, using a dominant negative form of PI3K, results in longer larval growth periods and larger adults due to slower ecdysone release and delayed onset of pupariation. More recently it has been shown that Target of Rapamycin (TOR) may link the ecdysone-regulated development to the PI3K mediated growth pathways (Layalle, Arquier, and Leopold 2008; reviewed in (Nijhout 2008)).

The levels of ecdysone release are therefore inversely proportional to larval growth and adult body size; with early onset of the ecdysone peak giving small flies and reduced ecdysone prolonging the growth period to give larger adults. Thus the time spent in the larval growth phase is a critical determinant of body size, with longer growth periods resulting in more cell division cycles and delayed onset of differentiation. In the next section we address the question of how the ecdysone pulse works to affect rates of cell growth and cell cycle progression within specific larval tissues. In particular we discuss the developmental signalling pathways implicated in linking cell cycle patterning of larval imaginal tissues to the ecdysone titre.
