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Introduction
Annick Sawala currently works as a senior postdoc in the Physiology and Metabolism Lab, The Francis Crick Institute. Her current research is focused on growth control by nutrition, and on sex differences in metabolism and growth regulation.
She uses a combination of in vivo genetics, metabolomics and cell culture approaches to investigate the metabolic and signaling mechanisms that enable some organs, but not others, to grow during severe nutrient restriction. She is also investigating how the sex of an animal influences its growth.
Additional affiliations
February 2013 - March 2017
September 2007 - January 2012
Position
- PhD Student
Description
- My PhD investigated the regulation of BMP signalling by collagen IV and by integrin signalling, using primarily the early Drosophila embryo as an in vivo model system, but also including some work with zebrafish and Drosophila cell culture.
Education
September 2004 - September 2007
Publications
Publications (38)
Within a 3D tissue, cells need to integrate signals from growth factors, such as BMPs, and the extracellular matrix (ECM) to coordinate growth and differentiation. Here, we use the Drosophila embryo as a model to investigate how BMP responses are influenced by a cell's local ECM environment. We show that integrins, which are ECM receptors, are abso...
In the Drosophila embryo, formation of a bone morphogenetic protein (BMP) morphogen gradient requires transport of a heterodimer of the BMPs Decapentaplegic (Dpp) and Screw (Scw) in a protein shuttling complex. Although the core components of the shuttling complex--Short Gastrulation (Sog) and Twisted Gastrulation (Tsg)--have been identified, key a...
Cell growth and proliferation depend upon many different aspects of lipid metabolism. One key signaling pathway that is utilized in many different anabolic contexts involves Phosphatidylinositide 3-kinase (PI3K) and its membrane lipid products, the Phosphatidylinositol (3,4,5)-trisphosphates. It remains unclear, however, which other branches of lip...
The measurement of absolute metabolite concentrations in small samples remains a significant analytical challenge. This is particularly the case when the sample volume is only a few microlitres or less and cannot be determined accurately via direct measurement. We previously developed volume determination with two standards (VDTS) as a method to ad...
The confusingly named growth-blocking peptides are nutrient-dependent adipokines that stimulate insulin secretion and boost growth in developing flies. In this issue of Developmental Cell, Meschi et al. (2018) show that these adipose tissue-derived factors regulate insulin secretion by silencing a pair of inhibitory neurons that synapse with insuli...
Sexual size dimorphism (SSD), a sex difference in body size, is widespread throughout the animal kingdom, raising the question of how sex influences existing growth regulatory pathways to bring about SSD. In insects, somatic sexual differentiation has long been considered to be controlled strictly cell-autonomously. Here, we discuss our surprising...
Sexual dimorphisms in body size are widespread throughout the animal kingdom but their underlying mechanisms are not well characterized. Most models for how sex chromosome genes specify size dimorphism have emphasized the importance of gonadal hormones and cell-autonomous influences in mammals versus strictly cell-autonomous mechanisms in Drosophil...
Mid-L2 and early-L3 larvae show no sex differences in insulin signalling.
(A-B) Immunostaining for Ilp2 levels in insulin producing cells (IPCs) in mid-L2 (A) and early L3 (B) larvae. Ilp2 quantifications show mean, SD and individual data points for each CNS (see Materials and methods). C) Western blot for phospho-Akt, Akt and tubulin in whole body...
Sxl knockdown in oenocytes or midgut does not affect female body size and SSD.
(A) Body mass of wandering L3 larvae expressing Sxl RNAi in oenocytes using PromE-Gal4. Graph shows mean, SD and individual data points. (B) Body mass of wandering L3 larvae expressing Sxl RNAi in midgut enterocytes using Mex1-Gal4. Graph shows mean body mass and SD for...
Loss of neuronal Sxl expression following knockdown of Sxl and msl-2 or Sxl alone.
(A) Sxl immunostaining in the early L3 thoracic ventral nerve cord of control, elavc155>Sxl RNAi and and elavc155>Sxl RNAi + msl-2 RNAi larvae. DNA is labelled by DAPI. (B) Quantification of Sxl expression (mean signal intensity) in regions of interest similar to tho...
Expression patterns of Ilp2-Gal4 and Ilp2-lexA drivers used in this study.
Confocal Z-projections of the CNSs from female late L3 larvae showing expression of membrane-targeted GFP (UAS-CD8::GFP or lexAOP-CD2::GFP) in green and DNA stained by DAPI in blue. Ilp2-Gal4 and Ilp215-1-Gal4 are weakly active in some neurons of the ventral nerve cord (VNC)...
Restoration of Sxl in IPCs rescues the SSD phenotype of Ilp2>Sxl RNAi larvae.
(A-C) Single confocal sections through clusters of IPCs from female larvae, immunostained for Sxl and Ilp2 (to mark IPCs), with DNA stained by DAPI (blue). Sxl in the nuclei of IPCs is strongly expressed in control females (A) but absent in those of Ilp2-Gal4>UAS-Sxl RNAi...
Sxl, tra and tra-2 manipulations in the fat body have minor effects on female body size and SSD.
(A-B) Body mass of wandering L3 larvae expressing tra RNAi in the fat body using Cg-Gal4. (A) shows mean body mass per larva in mg (weighed in groups of n = 6–14 larvae) and (B) shows mean body mass and SD of individually weighed larvae (n = 27–30 larva...
Neuronal knockdown of Sxl abolishes the establishment of larval body SSD.
(A) Body mass of control and elavc155>Sxl RNAi 1 larvae at 3-24h after synchronization at the L1/L2 molt. Early L3 occurs at ~24h after L1/L2 molt. Mean body mass and SD was measured for replicate groups of 3–6 larvae (3h, 6h and 11h time points) or for individual larvae (18h...
Sxl does not function in glia to control larval body SSD.
(A) Confocal image projection of a late third instar larval CNS, with elavc155-Gal4-expressing cells permanently marked with GFP (green) and glial cells stained by anti-Repo antibody (red). There is no detectable overlap between elavc155-Gal4 driver activity and Repo signal. (B) Confocal ima...
amon386Y-Gal4 and VGAT-Gal4 but not Gad1-Gal4 are expressed in IPCs.
Confocal Z-projections of CNSs from late L3 larvae. UAS-CD8::GFP expression reveals that amon386Y-Gal4 (A) and VGAT-Gal4 (B) but not Gad1-Gal4 (C) are expressed in IPCs (marked by anti-Ilp2 immunostaining, Ilp2 also marks IPC projections in the corpora cardiaca of the ring gland,...
Cell-autonomous SSD contributions of Sxl and tra in the wing imaginal disc and larval fat body.
(A-B) nubbin-Gal4 driving expression of UAS-Sxl RNAi 1, UAS-tra RNAi 1, UAS-TraF or UAS-InR RNAi decreases the SSD of the wing pouch. Gal4-expressing cells in the wing pouch were marked by UAS-RFP. To measure cell-autonomous effects, the mean ratios and...
Underlying data for main and supporting figures.
In this Excel file, separate worksheets contain the data used in each figure panel as indicated.
(XLSX)
SSD screen of Gal4 drivers using UAS-Sxl RNAi.
Females of the genotype UAS-Sxl RNAi 1/CyO, Dfd-YFP; UAS-Dcr2 were crossed to control or Gal4 driver males but, for Gal4 drivers located on the X-chromosome, the cross was reversed. Wandering L3 larvae were sorted by sex and YFP expression into UAS-Sxl RNAi 1versus CyO, Dfd-YFP genotypes. Mean body mas...
Expression patterns of the Gad1-GAL4 and VGAT-GAL4 drivers in this study.
Confocal Z-projections of the CNSs from late L3 larvae showing Gad1-GAL4 (A) or VGAT-GAL4 (B) driving expression of membrane-targeted GFP (UAS-CD8::GFP) in green. DNA is stained by DAPI in blue.
(TIF)
SSD phenotypes of Sxl knockdown with Ilp215-1-Gal4, VGAT-Gal4 or amon386Y-Gal4 are not altered by blocking Gal4 activity in VNC neurons with tsh-Gal80.
(A) CNS expression patterns in female larvae at late L3 of Ilp215-1-Gal4, VGAT-Gal4 or amon386Y-Gal4 driving UAS-CD8::GFP (green) in the absence (left) or presence (right) of tsh-Gal80. All images s...
Male and female larvae differ in absolute but not mass-specific food intake.
Absolute (per larva) and mass-specific (per mg of larval body mass) food intake in early L2 and early L3 larvae, measured during 20 min (early L2) or 25 min (early L3) in groups of 9–20 larvae. Graphs plot mean, SD and data points for individual replicates. P-values are sh...
Expression patterns of Gal4 drivers.
Expression patterns were examined in late L3 larvae, with Gal4 drivers activating the expression of UAS-CD8::GFP. For elavc155-Gal4, expression was examined using act>stop>Gal4, UAS-GFP/GlaBc; UAS-Flp/TM6 to permanently label Gal4-expressing cells. An X or listed structures indicates expression present in some o...
IPC and Ilp manipulations affecting Insulin signalling do not alter larval body SSD.
(A) IPC overexpression of UAS-Ilp2 or UAS-Ilp5 using a combination of Ilp2-GAL4 + Ilp215-3-Gal4 has no effect on body size or SSD. (B) IPC inhibition of PI3K signalling (UAS-p60 driven by Ilp2-GAL4 + Ilp215-3-Gal4) reduces body size in both males and females but it...
Female-biased expression of dmyc is maintained in elavc155>Sxl RNAi larvae.
Graph shows qPCR quantitation of dmyc transcript levels from whole early L3 larvae, normalised to the geometric mean of tubulin and RNA polymerase II transcript levels. Individual data points are shown for replicates normalised to the mean female value for each genotype and...
NR represses PI3K signaling more strongly in fat body than oenocytes.
Panels in top two rows show endogenous FoxO expression in fat body (left) and oenocytes (right, marked with PromE>mGFP) from Fed48 and NR66 larvae. Redistribution of FoxO from the cytoplasm to the nucleus (associated with decreased PI3K signaling) during NR is more pronounced in...
Quantitation of protein knockdowns with Acc, Kar, Cyp4g1 and Cpr RNAi.
(A) Antibody staining for Acc, Kar, Cyp4g1 and Cpr in oenocytes following PromE-GAL4 driven RNAi in NR larvae. Scale bar is 20μm. (B) Staining for Kar in nlsGFP positive Flp-out clones expressing Kar Ri in oenocytes. Scale bar is 10μm. (C) Graph of relative immunostaining intens...
Genetic interactions between FarO and PI3K.
(A) In Fed48 larvae, PromE>Dp110DN induces a low level of oenocyte lipid droplets that are suppressed in PromE>FarO Ri Dp110DN. In NR larvae, PromE>Dp110DN does not noticeably alter lipid droplet induction and thus inhibition of NR droplet induction is similar in PromE>FarO Ri and in PromE>FarO Ri Dp110DN...
FarO and Kar do not limit the size of oenocytes at the late larval stage.
(A) Neither Kar nor FarO RNAi detectably alter lipid droplets in the fat body. Flp-out clones for Kar RNAi (top row) or FarO RNAi (bottom row), marked with nlsGFP, show no detectable change in lipid droplets (LipidTOX), nuclear size or cell size in NR larvae. Nuclei are marke...
Kar but not FarO RNAi significantly increases oenocyte membrane p-Akt.
(A, B) Quantitation of membrane p-Akt intensity, relative to the control genotype, in NR oenocytes expressing FarO RNAi (A) or Kar RNAi (B). Membrane p-Akt intensity increases 1.7 fold with Kar RNAi but does not change significantly with FarO RNAi. (C) Panels show p-Akt staining...
Quantitations of cell size and membrane p-Akt expression.
(A, B) Fat body cell areas in Flp-out clones. Dp110 overexpression increases cell size relative to controls in NR larvae (A) and Dp110DN expression decreases cell size relative to controls in Fed48 larvae (B). (C, D) Quantitation of Oenocyte membrane p-Akt expression. Membrane p-Akt expressi...
Quantitations of neutral lipid content.
The relative lipid contents, calculated from neutral LipidTOX stainings, for experiments shown in the main Figures. (A,B) Flp-out clones in the fat body expressing Dp110 in NR (A) or Dp110DN in Fed48 larvae (B). (C-E) PromE-GAL4 controls in Fed48 and NR larvae (C) and PromE-GAL4 driven expression of Dp110 or...
Ilp6 is not required for NR induction of lipid droplets in larval oenocytes.
Clusters of oenocytes from NR larvae, marked with streptavidin-A555 and showing lipid droplets (LipidTOX) and nuclei (DAPI). (A) Larvae deficient for Ilp6 (Df(1)Ilp6) show lipid droplet induction similar to controls (w1118). (B) Larvae with fat body-specific RNAi knockdown...
Members of the Tolloid family of metalloproteinases liberate BMPs from inhibitory complexes to regulate BMP gradient formation during embryonic dorsal-ventral axis patterning. Here, we determine mechanistically how Tolloid activity is regulated by its non-catalytic CUB domains in the Drosophila embryo. We show that Tolloid, via its N-terminal CUB d...
Bone morphogenetic proteins (BMPs) are synthesized as proproteins that undergo proteolytic processing by furin/subtilisin proprotein convertases to release the active ligand. Here we study processing of BMP5/6/7/8 proteins, including the Drosophila orthologs Glass Bottom Boat (Gbb) and Screw (Scw) and human BMP7. Gbb and Scw have three functional f...
