Summary
Body size and the timing of metamorphosis are two important interlinked life-history traits that define holometabolous insect development. Metamorphic timing is largely controlled by a neuroendocrine signaling axis composed of the ecdysone (E) producing prothoracic gland (PG) and its presynaptic neurons (PGNs) that produce prothoracicotropic hormone (PTTH). Despite the well-characterized role for PTTH and its receptor tyrosine kinase (RTK) Torso in mediating proper metamorphic timing, recent studies in Drosophila indicate that additional unidentified PGN-derived tropic factor(s) exist that provide additional timing cues. Here we identify Alk and Pvr, as two additional RTKs which function in coordination with PTTH/Torso signaling to regulate E synthesis, pupariation timing and body size. Similar to Torso, both Alk and Pvr trigger Ras/Erk signaling in the PG to upregulate expression of E biosynthetic enzymes, while Alk also suppresses autophagy induction by activating Pi3K/Akt. The Alk ligand Jeb is produced by the PGNs and serves as an additional PGN-derived tropic factor. The Pvr ligand Pvf3 is also produced by the PGNs, but the activation of Pvr mainly relies on autocrine signaling by PG-derived Pvf2 and Pvf3. These findings illustrate that a multitude of juxtracrine and autocrine signaling systems have evolved to regulate the timing of metamorphosis, the defining event of holometabolous development.
Competing Interest Statement
The authors have declared no competing interest.