title: New X-chromosomal interactors of dFMRP regulate axonal and synaptic morphology of brain neurons inDrosophila melanogaster.
abstract: Fragile X syndrome is a neuro-developmental disease caused by transcriptional inactivation of the gene FMR1 (fragile X mental retardation 1) and loss of its protein product FMRP. FMRP has multiple neuronal functions which are implemented together with other proteins. To better understand these functions, the aim of this study was to reveal new protein interactors of dFMRP. In a forward genetic screen, we isolated ethyl-metanesulphonate-induced X-chromosomal modifier mutations ofdfmr1. Four of them were identified and belong to the genes:peb/hindsight,rok,shaggyandras. They are dominant suppressors of thedfmr1 overexpression wing phenotype 'notched wings'. These mutations dominantly affected the axonal and synaptic morphology of the lateral ventral neurons (LNv's) in adultDrosophilabrains. Heterozygotes for each of them displayed effects in the axonal growth, pathfinding, branching and in the synapse formation of these neurons. Double heterozygotes for bothdfmr1-null mutation and for each of the suppressor mutations showed robust genetic interactions in the fly central nervous system. The mutations displayed severe defects in the axonal growth and synapse formation of the LNv's in adult brains. Our biochemical studies showed that neither of the proteins - Rok, Shaggy, Peb/Hnt or Ras - encoded by the four mutated genes regulates the protein level of dFMRP, but dFMRP negatively regulates the protein expression level of Rok in the brain. Altogether, these data suggest that Rok, Shaggy, Peb/Hnt and Ras are functional partners of dFMRP, which are required for correct wing development and for neuronal connectivity inDrosophilabrain.
authors.affiliation: Faculty of Biology, Sofia University 'St. Kliment Ohridski' , Sofia , Bulgaria.
authors.forename: Dimitrina
authors.initials: D
authors.lastname: Georgieva
authors.affiliation: Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Roumen
authors.initials: R
authors.lastname: Dimitrov
authors.affiliation: Faculty of Biology, Sofia University 'St. Kliment Ohridski' , Sofia , Bulgaria.
authors.forename: Meglena
authors.initials: M
authors.lastname: Kitanova
authors.affiliation: Faculty of Biology, Sofia University 'St. Kliment Ohridski' , Sofia , Bulgaria.
authors.forename: Ginka
authors.initials: G
authors.lastname: Genova
keywords: brain axon; dfmr1; peb/hnt; ras; rok; sgg; synaptic morphology