Genetic analysis of two mutations that affect neural-specific glycosylation

Abstract

Complex carbohydrate expression regulates cell-cell interactions that can affect development and normal tissue function. Human genetic disorders that affect glycosylation often result in mental retardation and an overall failure to thrive. In Drosophila melanogaster, the HRP-epitope is an example of a neural specific N-linked oligosaccharide that provides opportunities for identifying mechanisms that control glycosylation and identifying mutations that affect glycosylation. Screening for new genes necessary for HRP-epitope expression has begun to identify important regulatory factors by generating mutants. One mutant, called sff, and another mutant, called MS-16, have decreased levels of expression of the HRP-epitope in neural tissue. In addition, the adult mutants show abnormal behavioral characteristics that include failure to escape in a sufficient amount of time and the tendency to congregate at the bottom of the vial even when there is a possibility to escape. By following the HRP-epitope expression in embryos from crosses of mutants to chromosomal deletions, we will characterize the genetic loci that interact with sff on the second chromosome and perform a genetic mapping of the mutation in MS-16 on the second chromosome. Additionally, we will seek how these mutations interact with the tollo pathway, which has previously been shown to modulate expression of the HRP-epitope. After an analysis of the phenotypes associated with the functions of sff and MS-16, we will then be able to assess neuromuscular development, embryonic neurological development, viability, fertility, and adult behavior.