Regulation of Body Size and Growth Control

Abstract

The control of body and organ growth is essential for the development of adults with proper size and proportions, which is important for survival and reproduction. In animals, adult body size is determined by the rate and duration of juvenile growth, which are influenced by the environment. In nutrient-scarce environments in which more time is needed for growth, the juvenile growth period can be extended by delaying maturation, whereas juvenile development is rapidly completed in nutrient-rich conditions. This flexibility requires the integration of environmental cues with developmental signals that govern internal checkpoints to ensure that maturation does not begin until sufficient tissue growth has occurred to reach a proper adult size. The Target of Rapamycin (TOR) pathway is the primary cell-autonomous nutrient sensor, while circulating hormones such as steroids and insulin-like growth factors are the main systemic regulators of growth and maturation in animals. We discuss recent findings in Drosophila melanogaster showing that cell-autonomous environment and growth-sensing mechanisms, involving TOR and other growth-regulatory pathways, that converge on insulin and steroid relay centers are responsible for adjusting systemic growth, and development, in response to external and internal conditions. In addition to this, proper organ growth is also monitored and coordinated with whole-body growth and the timing of maturation through modulation of steroid signaling. This coordination involves interorgan communication mediated by Drosophila insulin-like peptide 8 in response to tissue growth status. Together, these multiple nutritional and developmental cues feed into neuroendocrine hubs controlling insulin and steroid signaling, serving as checkpoints at which developmental progression toward maturation can be delayed. This review focuses on these mechanisms by which external and internal conditions can modulate developmental growth and ensure proper adult body size, and highlights the conserved architecture of this system, which has made Drosophila a prime model for understanding the coordination of growth and maturation in animals.

Control of Cell Growth and Proliferation by the Tribbles Pseudokinase: Lessons from Drosophila

“…In the United States, 27% of adults and up to 50% of children have been diagnosed as severely obese and world-wide, TD2M diagnoses have grown to epidemic proportions [ 96 , 97 ]. Drosophila models of diet-induced obesity, insulin resistance, hyperglycemia, and hyperinsulinemia have been used to study the role of Trbl in modulating energy storage in response to dietary stress using two storage tissues analogous to the liver and adipose tissues of mammals: (1) the larval fat body, a repository of fats and proteins, the fat body sustains tissue rebuilding during the non-feeding stages of metamorphosis, and (2) the adult fat body, which develops independently to store nutrients required to fuel energy-expensive adult behaviors including flight and gametogenesis [ 98 , 99 ].…”

The gut hormone Allatostatin C regulates food intake and metabolic homeostasis under nutrient stress

“…We next sought to determine whether EECs sense and respond directly to levels of nutrients and relay availability systemically through release of AstC. We thus acutely inhibited in the EECs the activity of the Target of Rapamycin (TOR) pathway, a primary mediator of cell-autonomous nutrient sensing 8 , by overexpressing the TOR-inhibitory proteins Tuberous Sclerosis Complex 1 and 2 (TSC1/2) 36 . This manipulation mimics nutrient deprivation in these cells in an otherwise nutrition-replete animal.…”

“…5E). Retention of AstC under fed conditions requires the activity of the intracellular nutrient sensor TOR, which is promoted by nutrients, particularly amino acids 8 . AstC acts directly upon the APCs, which express the receptor AstC-R2, to promote AKH release.…”

“…Under conditions of nutrient scarcity, mammalian glucagon induces the mobilization of stored energy to provide the means to sustain glycemic control and basic physiological body functions. Likewise, flies express several conserved insulin-like peptides (DILPs) in insulin-producing cells (IPCs) of the brain, which are believed to be functionally and evolutionarily related to mammalian pancreatic b cells 8,9 . During nutrient abundance, these DILPs promote growth and metabolism through their activation of a single insulin receptor.…”

Transporter-mediated ecdysteroid trafficking across cell membranes: A novel target for insect growth regulators

“…7) More recently, application of the molecular genetic tools in the fruit fly Drosophila melanogaster has particularly contributed to the accumulation of knowledge about physiological processes that are both upstream and downstream of ecdysteroid signaling. [8][9][10] Moreover, besides basic biological studies, applied aspects of ecdysteroid signaling have also been extensively investigated in various insect species, in order to develop novel insect growth regulators (IGRs). 11,12) For example, diacylhydrazine (DAH)based non-steroidal ecdysone agonists that target the ecdysone receptor (EcR) have been developed and used as IGRs for over 30 years.…”