Body building: regulation of shape and size by PI3K/TOR signaling during development

Abstract

Growth of organisms and their constituent parts responds to both intrinsic and extrinsic cues during development: organisms of a given species generally grow at a predictable rate and to a specific body size, but individuals can modify this program during development in response to environmental conditions. Recent experiments, using gene knockouts and targeted overexpression, have revealed the central role of a signaling network controlled by the PI3K and TOR kinases in this regulation. These signaling molecules control growth by coordinately regulating a large number of cell biological processes. This review focuses on the cellular activities regulated by PI3K and TOR during development, and discusses how changes in different aspects of cellular metabolism may interact to regulate growth.

MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1 activity in the size control of the Xenopus kidney

“…S2). Akt phosphorylation is a key event in regulating mTORC1 signaling (17)(18)(19), an important pathway in organ size control (20,21). Whole-mount in situ hybridizations confirmed that mTORC1 signaling components are expressed in the pronephric kidney (Fig.…”

“…The fact that the growth of the proximal tubules could be inhibited by LY294002 (Fig. 2 N and O) prompted us to investigate Insulin and Igf signaling, an evolutionarily conserved pathway regulating overall body and organ size (20,21,(28)(29)(30). Whereas Insulin and Igf receptors and the downstream signaling intermediate Irs1 were expressed throughout the embryo, two ligands, Insulin and Igf2 mRNAs, were specifically expressed in the proximal tubules of the kidney at stage 38 ( Fig.…”

Size and shape: the developmental regulation of static allometry in insects

“…It is sensed directly by dividing cells and suppresses the insulin-signaling pathway through an unknown mechanism via dTOR (target of rapamycin). (28,29) Nutrition also regulates the insulin-signaling pathway indirectly, through a reduction in the release of dILPs from neurosecretory cells in the brain, (24) and through an unknown humeral mechanism via the fat body (the insect equivalent of the liver). (30) Finally, the insulin signaling pathway is also regulated by other hormones, for example ecdysone, (31)(32)(33) JH (34) and Imaginal Disk Growth Factors, (35) the release of which may also be nutritionally regulated.…”

“…(28,29) This is theoretically sufficient to control the allometric relationship between organ size and body size. (70) However, the nutritional allometries of organ size against body size cannot simply be a consequence of both independently responding to what the developing insect is eating.…”

Regulation of cell growth by autophagy

“…[1][2][3] Cellular mechanisms for degrading aberrant, damaged constituents of cytosol involve the non-lysosomal ubiquitinproteasome system and autophagy, which is a lysosome-mediated process. 4 During autophagy, subcellular membrane structures are formed to sequester cargo into lysosomes for breakdown by acid hydrolases.…”