Image from Hudry et al, Nature (2016)

In our last journal club we discussed two very nice papers on sexual dimorphism in Drosophila intestines that controls growth, regeneration and lifespan:

The sexual identity of adult intestinal stem cells controls organ size and plasticity. Hudry B, Khadayate S, Miguel-Aliaga I. Nature. 2016 Feb 18;530(7590):344-8

Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction. Regan JC, Khericha M, Dobson AJ, Bolukbasi E, Rattanavirotkul N, Partridge L. Elife. 2016 Feb 16;5. pii: e10956.

In the first paper, Bruno Hudry (from the lab of Irene Miguel Aliaga) showed that female intestines showed both a marked increase in cell proliferation/regeneration in response to damage and in increase propensity to develop tumors. Both these effects were dependent on the sexual identity of the intestinal stem cells, which is controlled by Transformer expression.

The second paper from Jenny Regan described male:female differences in both intestinal pathology in aged guts and response to infection. Interestingly, this paper indicates that these differences are regulated by the sexual identity of the differentiated epithelial cells in the gut, although the differences do involve altered stem cell proliferation.

 We liked both papers a lot. Its a topic that we’ve become interested in – our former postdoc, Liz Rideout, recently published a paper on sex differences in insulin signaling and growth in Drosophila, and she’s continuing this work in her own lab at UBC.

In a recent lab journal club we discussed a very nice paper from Takashi Koyama and Christen Mirth:

Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation. (2016) PLoS Biology

Nutrients promote body growth in Drosophila by stimulating insulin signaling. One main way that this happens involves endocrine signaling between the fat body and the brain – in protein rich diets, amino acid import into fat body cells activates TOR and leads to release of a secreted factor(s) that acts on the brain to stimulate expression and release of insulin-like peptides (ILPs) from neurosecretory cells. However, the nature of the these AA-sensitive fat body factors has remained elusive. In this paper, the authors identify the Growth Blocking Peptides 1 and 2 (GBP1 and 2) as strong candidates. They show that expression of GBP1 and 2 is regulated by AA/TOR signaling and that both GBP1 and 2 are secreted from the fat body and can act directly on the brain to promote ILP release.

We liked this paper a lot. In particular we appreciated the rigorous and comprehensive approach the authors used to establish that both GBP1 and 2 are bona fide fat-body derived factors that respond to TOR signaling and that act directly on the brain to promote insulin release.

Last week in lab journal club we discussed a very nice paper by @mattpiperlab and @a_j_dobson available online on bioRxiv:

Lifespan extension by dietary restriction in Drosophila is associated with GATA motifs and organ-specific, TOR-dependent transcriptional networks.

Dietary restriction of amino acids and inhibition of TOR (by Rapamycin) are two robust ways to extend lifespan in flies. Here the authors do some very nice tissue mRNA expression analyses to examine how these two experimental manipulations may affect gene expression. Their data reveal some interesting tissue specific effects in transcription and also point to a role for GATA transcription factors in lifespan-associated transcriptional changes.

We liked this paper – it will open up lots of new work on GATA factors and nutrient/TOR signaling.  And we were especially happy to see it on bioRXiv for all to view. Some thoughts we had (mostly for future work): Does TOR signaling regulate the GATA transcription factors? Do these GATA factors regulate lifespan? Might they also be important for nutrient/TOR control of transcription and growth in larvae or do nutrients/TOR regulate two different transcriptional programs in larvae (growth) vs adult (fecundity and lifespan)?

This 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)