ABSTRACT
The ability to select a better option from multiple acceptable ones is important for animals to optimize their resources. The mechanisms that underlie such decision-making processes are not well understood. We found that selection of egg-laying site in Drosophila melanogaster is a suitable system to probe the neural circuit that governs simple decision-making processes. First, Drosophila females pursue active probing of the environment before depositing each egg, apparently to evaluate site quality for every egg. Second, Drosophila females can either accept or reject a sucrose-containing medium, depending on the context. Last, communication of the "acceptability" of the sucrose-containing medium as an egg-laying option to the reproductive system depends on the function of a group of insulin-like peptide 7 (ILP7)-producing neurons. These findings suggest that selection of egg-laying site involves a simple decision-making process and provide an entry point toward a systematic dissection of this process.
Subject(s)
Behavior, Animal , Decision Making , Drosophila melanogaster , Models, Animal , Neurons/physiology , Oviposition , Animals , Drosophila Proteins/metabolism , Drosophila melanogaster/physiology , Female , Neuropeptides/metabolismABSTRACT
Understanding the mechanisms through which multicellular organisms regulate cell, organ and body growth is of relevance to developmental biology and to research on growth-related diseases such as cancer. Here we describe a new effector in growth control, the small GTPase Rheb (Ras homologue enriched in brain). Mutations in the Drosophila melanogaster Rheb gene were isolated as growth-inhibitors, whereas overexpression of Rheb promoted cell growth. Our genetic and biochemical analyses suggest that Rheb functions downstream of the tumour suppressors Tsc1 (tuberous sclerosis 1)-Tsc2 in the TOR (target of rapamycin) signalling pathway to control growth, and that a major effector of Rheb function is ribosomal S6 kinase (S6K).
Subject(s)
Cell Division/genetics , Drosophila Proteins/metabolism , Growth Substances/metabolism , Monomeric GTP-Binding Proteins/physiology , Neuropeptides/physiology , Ribosomal Protein S6 Kinases/metabolism , Animals , Cell Division/physiology , Cell Size/genetics , Cell Size/physiology , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Eye/ultrastructure , Female , Gene Deletion , Genes, Insect , Genes, Tumor Suppressor , Growth Substances/genetics , Monomeric GTP-Binding Proteins/genetics , Neuropeptides/genetics , Ras Homolog Enriched in Brain Protein , Recombinant Fusion Proteins/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Ribosomal Protein S6 Kinases/genetics , Signal Transduction , Transcriptional Activation , TransgenesABSTRACT
BACKGROUND: The insulin/IGF-1 signaling pathway controls cellular and organismal growth in many multicellular organisms. In Drosophila, genetic defects in components of the insulin signaling pathway produce small flies that are delayed in development and possess fewer and smaller cells as well as female sterility, reminiscent of the phenotypes of starved flies. RESULTS: Here we establish a causal link between nutrient availability and insulin-dependent growth. We show that in addition to the Drosophila insulin-like peptide 2 (dilp2) gene, overexpression of dilp1 and dilp3-7 is sufficient to promote growth. Three of the dilp genes are expressed in seven median neurosecretory cells (m-NSCs) in the brain. These m-NSCs possess axon terminals in the larval endocrine gland and on the aorta, from which DILPs may be released into the circulatory system. Although expressed in the same cells, the expression of the three genes is controlled by unrelated cis-regulatory elements. The expression of two of the three genes is regulated by nutrient availability. Genetic ablation of these neurosecretory cells mimics the phenotype of starved or insulin signaling mutant flies. CONCLUSIONS: These results point to a conserved role of the neuroendocrine axis in growth control in multicellular organisms.