What determines organ size during development and regeneration?

The sizes of living organisms span over 20 orders of magnitude or so. This daunting observation could intimidate researchers aiming to understand the general mechanisms controlling growth. However, recent progress suggests the existence of principles common to organisms as diverse as fruit flies, mice and humans.

Inter-Organ Growth Coordination Is Mediated by the Xrp1-Dilp8 Axis in Drosophila.

How organs scale with other body parts is not mechanistically understood. We have addressed this question using the Drosophila imaginal disc model. When the growth of one disc domain is perturbed, other parts of the disc and other discs slow down their growth, maintaining proper inter-disc and intra-disc proportions.

[Some insulins to orchestrate growth].

Body size is an intrinsic property of living organisms that is intimately linked to the developmental program to produce fit individuals with proper proportions. Final size is the result of both genetic determinants and sophisticated mechanisms adapting size to available resources. Even though organs grow according to autonomous programs, some coordination mechanisms ensure that the different body parts adjust their growth with the rest of the body.

Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability.

Early transplantation and grafting experiments suggest that body organs follow autonomous growth programs [1-3], therefore pointing to a need for coordination mechanisms to produce fit individuals with proper proportions. We recently identified Drosophila insulin-like peptide 8 (Dilp8) as a relaxin and insulin-like molecule secreted from growing tissues that plays a central role in coordinating growth between organs and coupling organ growth with animal maturation [4, 5]. Deciphering the function of Dilp8 in growth coordination relies on the identification of the receptor and tissues relaying Dilp8 signaling.

The Systemic Control of Growth.

Growth is a complex process that is intimately linked to the developmental program to form adults with proper size and proportions. Genetics is an important determinant of growth, as exemplified by the role of local diffusible molecules setting up organ proportions. In addition, organisms use adaptive responses allowing modulating the size of individuals according to environmental cues, for example, nutrition.

Neuronal glycogen synthesis contributes to physiological aging.

Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells.

Mei-P26 mediates tissue-specific responses to the Brat tumor suppressor and the dMyc proto-oncogene in Drosophila.

TRIM-NHL proteins are a family of translational regulators that control cell growth, proliferation, and differentiation during development. Drosophila Brat and Mei-P26 TRIM-NHL proteins serve as tumor suppressors in stem cell lineages and have been proposed to exert this action, in part, via the repression of the protooncogene dMyc. Here we analyze the role of Brat, Mei-P26, and dMyc in regulating growth in Drosophila imaginal discs.

bantam miRNA promotes systemic growth by connecting insulin signaling and ecdysone production.

During the development of multicellular organisms, body growth is controlled at the scale of the organism by the activity of long-range signaling molecules, mostly hormones. These systemic factors coordinate growth between developing tissues and act as relays to adjust body growth in response to environmental changes [1]. In target organs, long-range signals act in concert with tissue-autonomous ones to regulate the final size of a given tissue.