Lab Journal Club: nutritional control of insulin expression in flies

UntitledThis week we discussed the following paper:

Signaling from Glia and Cholinergic Neurons Controls Nutrient-Dependent Production of an Insulin-like Peptide for Drosophila Body Growth (2015) Dev Cell, 35, 295

Naoki Okamoto and Takashi Nishimura


In this paper Okamoto and Nishimra describe how dILP5 mRNA expression is regulated by dietary nutrients (protein). This regulation relies on a relay mechanism involving nutrient-responsive glia, which locally secrete dILP6 to activate cholinergic neurons, which then secrete Jeb that activated the Alk receptor on the surface of IPCs, which then induce dILP5 expression in response to PI3K/Akt activation.

We liked this paper. We were interested in some of the parallels between how IPCs responded to nutrients to control dILP5 and how neuroblasts control their division in response to nutrients (in papers we have discussed in previous lab journal clubs). In both cases, an initial step is local dILP6 secretion from surface glia, however, in the case of neuroblast division, these glia respond to a fat-derived signal release in response to TOR activation (Chell, 2010; Sousa-Nunes, 2011). In this paper, activation of TOR in the fat body appears to be unnecessary. Instead the surface glia respond directly to amino acids and insulins. Similarly the Jeb-ALK pathway is also involved in controlling IPCs in neuroblasts. In this paper, ALK activation of IPCs is necessary to promote dILP5 expression in nutrient-rich conditions. In contrast ALK activation of neuroblasts is required to maintain their proliferation in late larval starvation (brain sparing – Cheng, 2011)

Lab XMas lunch

Lab Journal Club: Synchronizing organ growth and developmental timing

CD_Fruitfly01This week we discussed four great papers from the Leopold, Halme, Gontijo (@alisson_gontijo) and Dominguez labs.

They all described how Lgr3 is the receptor for dILP8, a factor secreted from damaged organs to limit ecdysone release and slow organismal development and growth. While each paper made the same discovery, they did differ in experimental approaches and in some of their findings (which is not a bad thing).

All four were great papers – hopefully they receive the similar wide recognition that they each deserve.

Garelli A, Heredia F, Casimiro AP, Macedo A, Nunes C, Garcez M, Dias AR, Volonte YA, Uhlmann T, Caparros E, Koyama T, Gontijo AM. Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing. Nat Commun. 2015 Oct 29;6:8732.

Colombani J, Andersen DS, Boulan L, Boone E, Romero N, Virolle V, Texada M, Léopold P. Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability. Curr Biol. 2015 Oct 19;25(20):2723-9.

Vallejo DM, Juarez-Carreño S, Bolivar J, Morante J, Dominguez M. A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3. Science. 2015 Nov 13;350(6262)

The relaxin receptor Lgr3 mediates growth coordination and developmental delay during Drosophila melanogaster imaginal disc regeneration. (2015) BioRxiv. Jacob S. Jaszczak, Jacob B. Wolpe, Rajan Bhandari, Rebecca G. Jaszczak, Adrian Halme




Recent lab journal clubs: flies, insulin, TOR and other good stuff


We’ve fallen behind a bit (a lot!) on posting our regular lab journal clubs. So here are some of the papers we’ve discussed over the last year or so.  What we liked about all these papers is that they each highlight the power and versatility of Drosophila genetics to answer important questions about physiology, metabolism and growth.

Sano H, Nakamura A, Texada MJ, Truman JW, Ishimoto H, Kamikouchi A, Nibu Y, Kume K, Ida T, Kojima M. The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster. PLoS Genet. 2015 May 28;11(5):e1005209.

Koyama T, Rodrigues MA, Athanasiadis A, Shingleton AW, Mirth CK. Nutritional control of body size through FoxO-Ultraspiracle mediated ecdysone biosynthesis. Elife. 2014 Nov 25;3. doi: 10.7554/eLife.03091

Rodenfels J, Lavrynenko O, Ayciriex S, Sampaio JL, Carvalho M, Shevchenko A, Eaton S. Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development. Genes Dev. 2014 Dec 1;28(23):2636-51.

Brankatschk M, Dunst S, Nemetschke L, Eaton S. Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling. Elife. 2014 Oct 2;3.

Tiebe M, Lutz M, De La Garza A, Buechling T, Boutros M, Teleman AA. REPTOR and REPTOR-BP Regulate Organismal Metabolism and Transcription Downstream of TORC1. Dev Cell. 2015 May 4;33(3):272-84.

Kim J, Neufeld TP. Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3. Nat Commun. 2015 Apr 17;6:6846.

Chatterjee D, Katewa SD, Qi Y, Jackson SA, Kapahi P, Jasper H. Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):17959-64

Hasygar K, Hietakangas V. p53- and ERK7-dependent ribosome surveillance response regulates Drosophila insulin-like peptide secretion. PLoS Genet. 2014 Nov 13;10(11):e1004764.

Sun X, Wheeler CT, Yolitz J, Laslo M, Alberico T, Sun Y, Song Q, Zou S. A mitochondrial ATP synthase subunit interacts with TOR signaling to modulate protein homeostasis and lifespan in Drosophila. Cell Rep. 2014 Sep 25;8(6):1781-92.

Ulgherait M, Rana A, Rera M, Graniel J, Walker DW. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Rep. 2014 Sep 25;8(6):1767-80.

Park S, Alfa RW, Topper SM, Kim GE, Kockel L, Kim SK. A genetic strategy to measure circulating Drosophila insulin reveals genes regulating insulin production and secretion. PLoS Genet. 2014 Aug 7;10(8):e1004555.