Gruber, L. | Search bioRxiv

bioRxiv2022

Diversification of neuropil organization in specialized and broadly tuned olfactory glomerular circuits in Drosophila melanogaster

In the Drosophila olfactory system most odorants are encoded in the antennal lobe in a combinatory way, activating several glomerular circuits. However, odorants of particular ecological role for the fly are encoded through activation of a single specialized olfactory pathway. Comparative analyses of densely reconstructed connectomes of one broadly tuned glomerulus (DL5) and one narrowly tuned glomerulus (DA2) gained detailed insight into the variations of synaptic circuitries of glomeruli with different computational tasks. Our approach combined laser-branding of glomeruli of interest with volume based focused ion beam-scanning electron microscopy (FIB-SEM) to enable precise targeting and analysis of the two glomeruli. We discovered differences in their neuronal innervation, synaptic composition and specific circuit diagrams of their major cell types: olfactory sensory neurons (OSNs), uniglomerular projection neurons (uPNs) and multiglomerular neurons (MGNs). By comparing our data with a previously mapped narrowly tuned glomerulus (VA1v), we identified putative generic features of narrowly tuned glomerular circuits, including higher density of neuronal fibers and synapses, lower degree of OSN lateralization, stronger axo-axonic connections between OSNs, dendro-dendritic connections between many uPNs, and lower degree of presynaptic input on OSN axons. In addition, this work revealed that the dendrites of the single uPN in DL5 contain a substantial amount of autapses interconnecting distant regions of the dendritic tree. The comparative analysis of glomeruli allows to formulate synaptic motifs implemented in olfactory circuits with different computational demands.

neuroscience↗

bioRxiv2020

Ether lipid and sphingolipid expression patterns are G-protein coupled estrogen receptor 1-dependently altered in breast cancer cells

Identifying co-expression of lipid species is challenging, but indispensable to identify novel therapeutic targets for breast cancer treatment. Lipid metabolism is often dysregulated in cancer cells, and changes in lipid metabolism affect cellular processes such as proliferation, autophagy, and tumor development. In addition to mRNA analysis of sphingolipid metabolizing enzymes, we performed liquid chromatography time-of-flight mass spectrometry analysis in three breast cancer cell lines. These breast cancer cell lines differ in estrogen receptor and G-protein coupled estrogen receptor 1 status. Our data show that sphingolipids and non-sphingolipids are strongly increased in SKBr3 cells. SKBr3 cells are estrogen receptor negative and G-protein coupled estrogen receptor 1 positive. Treatment with G15, a G-protein coupled estrogen receptor 1 antagonist, abolishes the effect of increased sphingolipid and non-sphingolipid levels in SKBr3 cells. In particular, ether lipids are expressed at much higher levels in cancer compared to normal cells and are strongly increased in SKBr3 cells. Our analysis reveals that this is accompanied by increased sphingolipid levels such as ceramide, sphingadiene-ceramide and sphingomyelin. This shows the importance of focusing on more than one lipid class when investigating molecular mechanisms in breast cancer cells. Our analysis allows unbiased screening for different lipid classes leading to identification of co-expression patterns of lipids in the context of breast cancer. Co-expression of different lipid classes could influence tumorigenic potential of breast cancer cells. Identification of co-regulated lipid species is important to achieve improved breast cancer treatment outcome. HighlightsO_LILC-HRMS analysis allows identification of co-expression between lipid classes C_LIO_LIPutative co-expression of sphingolipid and non-sphingolipid classes C_LIO_LIEther lipids are strongly upregulated in SKBr3 cells (ER negative, GPER1 positive) C_LI

cancer biology↗