Mutations in a phylogenetically ancient synaptic gene cause early lethality in Drosophila melanogaster


Meeting Abstract

P1-76  Sunday, Jan. 4 15:30  Mutations in a phylogenetically ancient synaptic gene cause early lethality in Drosophila melanogaster BAKER, JD*; RYAN, EG; KOWALCYZK, CP; GASIOREK, IS; MAY, HE; KAUTZ, M; NAIR, J; University of Miami; University of Miami; University of Miami; University of Miami; University of Miami; University of Miami; University of Miami bakerjd@bio.miami.edu

Neurons and synapses are thought to have evolved well after metazoan life emerged, yet ancestrally derived animals, such as sponges, have many genes known for their roles in synapse development or function. One example of these, the cript gene, is highly conserved across phylogeny with likely orthologs present in some plants. To date studies of Cript protein have focused on its role in binding the third PDZ domain of Post Synaptic Density Protein 95 (PSD95) and microtubules. Mutations of the CRIPT gene in humans are a cause of Primordial Dwarfism, a severe syndromic form of dwarfism. We chose to ask what the non-neuronal functions of this gene might be by mutagenizing the cript locus in Drosophila melanogaster and studying the consequent phenotypes. Using transposon induced excision mutagenesis we recovered 5 independent alleles that fall into distinct phenotypic classes. Four alleles die as early embryos showing defects at or before gastrulation. The remaining allele survives to the late larval/early pupal stages, with a prolonged larval period, and large larval body size. Intriguingly this allele may phenocopy mutations in discs large (dlg) the fly ortholog of psd95. Ongoing experiments include sequencing of alleles, transgenic rescue, fluorescent tagging of cript and detailed cellular analysis of the mutants to elucidate the cellular and molecular bases of the observed phenotypes.

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