From seconds to days: Neural plasticity viewed through a lipid lens.

Many adult neurons are dynamically remodeled across timescales ranging from the rapid addition and removal of specific synaptic connections, to largescale structural plasticity events that reconfigure circuits over hours, days, and months. Membrane lipids, including brain-enriched sphingolipids, play crucial roles in these processes. In this review, we summarize progress at the intersection of neuronal activity, lipids, and structural remodeling.

Glial control of sphingolipid levels sculpts diurnal remodeling in a circadian circuit.

Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes, with attendant reorganization of the cytoskeleton and membranes. Although cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce glucocerebrosidase (GBA) to locally catabolize sphingolipids.

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis.

Epithelial tissues robustly respond to internal and external stressors via dynamic cellular rearrangements. Cell extrusion acts as a key regulator of epithelial homeostasis by removing apoptotic cells, orchestrating morphogenesis, and mediating competitive cellular battles during tumorigenesis. Here, we delineate the diverse functions of cell extrusion during development and disease.

Breaking Down Neighbors to Fuel Tumorigenesis.

Autophagy supports cell growth and survival autonomously by recycling intracellular proteins and/or organelles. Reporting in Nature, Katheder and colleagues (2017) find that tumors trigger non-autonomous autophagy in neighboring cells and distant organs, thus fueling tumor growth and metastasis. This opens new avenues for understanding and manipulating cancers through cell-cell communication.

Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia.

Cells dynamically interact throughout animal development to coordinate growth and deter disease. For example, cell-cell competition weeds out aberrant cells to enforce homeostasis. In Drosophila, tumorigenic cells mutant for the cell polarity gene scribble (scrib) are actively eliminated from epithelia when surrounded by wild-type cells.

Non-autonomous overgrowth by oncogenic niche cells: Cellular cooperation and competition in tumorigenesis.

Tumor progression is classically viewed as the Darwinian evolution of subclones that sequentially acquire genetic mutations and autonomously overproliferate. However, growing evidence suggests that tumor microenvironment and subclone heterogeneity contribute to non-autonomous tumor progression. Recent Drosophila studies revealed a common mechanism by which clones of genetically altered cells trigger non-autonomous overgrowth.