Abstract: Proper development of all multi-cellular organisms requires not only correct spatial control of cellular interactions, but also correct timing of specific developmental programs of gene expression. Alterations in the timing of developmental pathway activity can significantly affect developmental outcomes including behavior, body size, reproduction, and aging. In insects, timing of developmental transitions, i.e., molting and metamorphosis, is mediated by pulses of the steroid hormone 20-hydroxyecdysone (20E). Prothoracicotropic hormone (PTTH) is thought to be the major brain-derived signal that controls the timing of 20E production in the prothoracic gland (PG), a major endocrine tissue of the larvae. Intriguingly, we find that PTTH signaling acts not only locally on the PG to stimulate 20E production, but also systemically on a subset of sensory neurons to program behavioral changes that likely facilitate the success of metamorphic process. Both these signaling events are mediated by Torso, a receptor tyrosine kinase that acts primarily through the MAPK/ERK kinase pathway. Although PPTH appears to play a critical role in ramping up biosynthesis of 20E prior to metamorphosis, we have also uncovered evidence that a separate signaling pathway, mediated by a G protein coupled receptor and involving several novel ABC transporters, is necessary to release ecdysone from the PG to achieve proper developmental timing. This new evidence challenges the conventional view that steroid hormones freely pass through membranes and instead suggests that regulated transport mechanisms exist to control steroid hormone entry and exit from cells.

References:

McBrayer, Z.*, Ono, H.*, Shimell, MJ*, Parvy, J.-P., Beckstead, R.B., Warren, J.T., Thummel, C.S., Dauphin-Villemant, C., Gilbert, L.I., and O’Connor, M.B. (2007) Prothoracicotropic hormone regulates developmental timing and body size in Drosophila. Dev. Cell 13: 857-871 PMID: 18061567

Rewitz K.F., Yamanaka, N., Gilbert, L.I. and O’Connor M.B. (2009) The insect neuropeptide PTTH activates the receptor tyrosine kinase Torso to initiate insect metamorphosis Science 326:1403-5 PMID: 19965758 This work is supported by NIH GM93301