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PMID:30002129

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Citation

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

Abstract

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.

Links

PubMed Online version:10.1242/dev.164111

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:ATE1

involved_in

GO:0071596: ubiquitin-dependent protein catabolic process via the N-end rule pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KIS4

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q7KIS4

involved_in

GO:0032877: positive regulation of DNA endoreduplication

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KIS4

enables

GO:0008418: protein-N-terminal asparagine amidohydrolase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q7KIS4

involved_in

GO:0060253: negative regulation of glial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KIS4

involved_in

GO:0071596: ubiquitin-dependent protein catabolic process via the N-end rule pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:TERA

involved_in

GO:0006530: asparagine catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:TERA

involved_in

GO:0045786: negative regulation of cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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