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- Luo, Jiangnan, et al.
(author)
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Insulin/IGF-Regulated Size Scaling of Neuroendocrine Cells Expressing the bHLH Transcription Factor Dimmed in Drosophila
- 2013
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:12
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Journal article (peer-reviewed)abstract
- Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS) in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the Drosophila CNS. By targeted genetic manipulations of insulin receptor (dInR) expression in a variety of neuron types we demonstrate that the cell size is affected only in neuroendocrine cells specified by the bHLH transcription factor DIMMED (DIMM). Several populations of DIMM-positive neurons tested displayed enlarged cell bodies after overexpression of the dInR, as well as PI3 kinase and Akt1 (protein kinase B), whereas DIMM-negative neurons did not respond to dInR manipulations. Knockdown of these components produce the opposite phenotype. Increased growth can also be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin) signaling components, such as Rheb (small GTPase), TOR and S6K (S6 kinase). After Dimm-knockdown in neuroendocrine cells manipulations of dInR expression have significantly less effects on cell size. We also show that dInR expression in neuroendocrine cells can be altered by up or down-regulation of Dimm. This novel dInR-regulated size scaling is seen during postembryonic development, continues in the aging adult and is diet dependent. The increase in cell size includes cell body, axon terminations, nucleus and Golgi apparatus. We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth.
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| 2. |
- Nässel, Dick R., et al.
(author)
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Factors that regulate insulin producing cells and their output in Drosophila
- 2013
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 4
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Research review (peer-reviewed)abstract
- Insulin-like peptides (ILPs) and growth factors (IGFs) not only regulate development, growth, reproduction, metabolism, stress resistance, and lifespan, but also certain behaviors and cognitive functions. ILPs, IGFs, their tyrosine kinase receptors and downstream signaling components have been largely conserved over animal evolution. Eight ILPs have been identified in Drosophila (DILP1-8) and they display cell and stage-specific expression patterns. Only one insulin receptor, dInR, is known in Drosophila and most other invertebrates. Nevertheless, the different DILPs are independently regulated transcriptionally and appear to have distinct functions, although some functional redundancy has been revealed. This review summarizes what is known about regulation of production and release of DILPs in Drosophila with focus on insulin signaling in the daily life of the fly. Under what conditions are DILP-producing cells (IPCs) activated and which factors have been identified in control of IPC activity in larvae and adult flies? The brain IPCs that produce DILP2, 3 and 5 are indirectly targeted by DILP6 and a leptin-like factor from the fat body, as well as directly by a few neurotransmitters and neuropeptides. Serotonin, octopamine, GABA, short neuropeptide F (sNPF), corazonin and tachykinin-related peptide have been identified in Drosophila as regulators of IPCs. The GABAergic cells that inhibit IPCs and DILP release are in turn targeted by a leptin-like peptide (unpaired 2) from the fat body, and the IPC-stimulating corazonin/sNPF neurons may be targeted by gut-derived peptides. We also discuss physiological conditions under which IPC activity may be regulated, including nutritional states, stress and diapause induction.
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