Hormonal regulation of mummy is needed for apical extracellular matrix formation and epithelial morphogenesis in Drosophila.

• Many epithelia produce apical extracellular matrices (aECM) that are crucial for organ morphogenesis or physiology. Apical ECM formation relies on coordinated synthesis and modification of constituting components, to enable their subcellular targeting and extracellular assembly into functional matrices. The exoskeleton of Drosophila, the cuticle, is a stratified aECM containing ordered chitin polysaccharide lamellae and proteinaceous layers, and is suited for studies of molecular functions needed for aECM assembly. Here, we show that Drosophila mummy (mmy) mutants display defects in epithelial organisation in conjunction with aberrant deposition of the cuticle and an apical matrix needed for tracheal tubulogenesis. We find that mmy encodes the UDP-N-acetylglucosamine pyrophosphorylase, which catalyses the production of UDP-N-acetylglucosamine, an obligate substrate for chitin synthases as well as for protein glycosylation and GPI-anchor formation. Consequently, in mmy mutants GlcNAc-groups including chitin are severely reduced and modification and subcellular localisation of proteins designated for extracellular space is defective. Moreover, mmy expression is selectively upregulated in epithelia at the time they actively deposit aECM, and is altered by the moulting hormone 20-Hydroxyecdysone, suggesting that mmy is part of a developmental genetic programme to promote aECM formation.

Nyckelord

Amino Acid Sequence

Animals

Chitin

metabolism

Drosophila

genetics

growth & development

metabolism

Drosophila Proteins

genetics

metabolism

Ecdysterone

biosynthesis

Epithelium

growth & development

metabolism

ultrastructure

Extracellular Matrix

metabolism

Gene Expression Regulation

Developmental

Gene Expression Regulation

Enzymologic

Genes

Insect

Insect Hormones

metabolism

Microscopy

Electron

Molecular Sequence Data

Morphogenesis

Mutation

Nucleotidyltransferases

genetics

metabolism

Protein Processing

Post-Translational

Sequence Homology

Amino Acid

Publikations- och innehållstyp

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