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Zülbahar, S, Sieglitz, F, Kottmeier, R, Altenhein, B, Rumpf, S and Klämbt, C (2018) Differential expression of Öbek controls ploidy in the blood-brain barrier. Development 145

During development, tissue growth is mediated by either cell proliferation or cell growth, coupled with polyploidy. Both strategies are employed by the cell types that make up the blood-brain barrier. During larval growth, the perineurial glia proliferate, whereas the subperineurial glia expand enormously and become polyploid. Here, we show that the level of ploidy in the subperineurial glia is controlled by the N-terminal asparagine amidohydrolase homolog Öbek, and high Öbek levels are required to limit replication. In contrast, perineurial glia express moderate levels of Öbek, and increased Öbek expression blocks their proliferation. Interestingly, other dividing cells are not affected by alteration of Öbek expression. In glia, Öbek counteracts fibroblast growth factor and Hippo signaling to differentially affect cell growth and number. We propose a mechanism by which growth signals are integrated differentially in a glia-specific manner through different levels of Öbek protein to adjust cell proliferation versus endoreplication in the blood-brain barrier.

PubMed Online version:10.1242/dev.164111

Amidohydrolases/metabolism; Animals; Asparaginase/genetics; Asparaginase/metabolism; Blood-Brain Barrier/cytology; Blood-Brain Barrier/embryology; Blood-Brain Barrier/metabolism; Cell Nucleus/metabolism; Cell Proliferation; Cell Survival; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/cytology; Drosophila melanogaster/embryology; Drosophila melanogaster/genetics; Embryo, Nonmammalian/cytology; Embryo, Nonmammalian/metabolism; Endoreduplication; Fibroblast Growth Factors/metabolism; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Genes, Insect; Models, Biological; Neuroglia/cytology; Neuroglia/metabolism; Ploidies; Signal Transduction