Chondroitin sulfate is required for the organ development and maintenance in Drosophila

Abstract

Heparan sulfate (HS) and chondroitin sulfate (CS) are evolutionary conserved glycosaminoglycans that are found in most animal species, including a genetically tractable model organism Drosophila. In contrast to extensive in vivo studies elucidating co-receptor functions of Drosophila HSPGs, only a limited number of studies have been conducted for those of CSPGs. This is partly due to the lack of in vivo model systems to systematically study the functions of Drosophila CSPGs in development. To investigate the global function of CS in development, we have generated mutants for Chondroitin synthase (Chsy), which encodes the Drosophila homologue of chondroitin synthase 1 (ChSy-1), via CRISPR-Cas9 mutagenesis. Our characterizations of the Chsy mutants indicated that a fraction of the mutants survive to adult stage, which allowed us to analyze the morphology of the adult organs. Chsy mutants exhibited a gradual disruption of the basement membrane (BM) and a subsequent degradation of the gross organ structure as mutant animals aged. The age-dependent decay of the ovary structure observed in the Chsy mutants suggests that normal CS function is required for the maintenance of the structural integrity of the ECM and gross organ architecture.