PgmNr D152: Body weight dependent autophagy induction mediates metamorphic timing control under nutrient restriction in Drosophila.

Authors:
Xueyang Pan 1,2 ; Michael O'Connor 1


Institutes
1) Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN; 2) Molecular, Cellular, Developmental Biology and Genetics Program, University of Minnesota, Minneapolis, MN.


Keyword: endocrine function

Abstract:

In Drosophila, the timing of post-embryonic developmental transitions are finely correlated with body growth, and also respond to environmental variants such as food availability. During L3 stage, fasting condition causes arrest of metamorphic transition when larvae do not reach a body weight threshold (critical weight), however, beyond the threshold metamorphosis is no longer postponed by starvation. It is well known that insulin/TOR signaling couples nutrient condition and metamorphic timing in prothoracic gland (PG), the larva endocrine organ making the molting hormone ecdysone. However, how larva body weight poses impact on metamorphic timing control, especially during nutrient deficiency, is not clearly understood.

In this study we find that macroautophagy (hearafter autophagy), a degradative cellular process found in various larva tissues, functions in PG as a body weight sensitive controller of metamorphosis during nutrient restriction (NR). We firstly detected autophagy induction in PG during NR, which tightly requires Atg genes and can be suppressed by insulin/TOR pathway. Intriguingly, NR-induced autophagy is only dynamic in early L3 stage but is gradually muted as larvae grow heavier. Upon autophagy suppression early L3 NR causes undersized larvae to pupariate precociously, leading to pupal lethality, whereas over-induction of autophagy causes developmental delay even in well fed larvae. Beyond confirming autophagy as a gatekeeper of metamorphosis, we further find that Anaplastic Lymphoma Kinase (Alk), a receptor tyrosine kinase, works as autophagy suppressor during late L3 NR. The Alk expression in PG keeps marginal until early L3 stage and boosts as larvae grow over the critical weight, indicating its functioning time window. Expression of constitutively active Alk in PG prevents NR-induced autophagy in early L3 stage, while knocking down Alk leaves autophagy markedly stimulated during late L3 NR. Besides autophagy, Alk activation larvae also phenocopy insulin pathway activation larvae on developmental timing and final body size, suggesting that Alk receptor may lead to similar signaling pathways to insulin receptor and thus compensate the loss of insulin signaling in PG during late L3 NR. In all, our findings uncover a novel view on how developmental timing is controlled in accordance with body growth.



Flybase Genetic Index:
1. FlyBase gene symbol: Alk; FBgn: FBgn0040505