1. The Drosophila agnostic Locus: Involvement in the Formation of Cognitive Defects in Williams Syndrome
- Author
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Nikitina Ea, E. V. Savvateeva-Popova, G. A. Zakharov, and A. V. Medvedeva
- Subjects
LIMK1 Gene ,Genetics ,learning ,biology ,WILLIAMS SYNDROME,LIMK1,DROSOPHILA,LOCOMOTOR ACTIVITY,LEARNING,MEMORY ,Williams syndrome ,Mutant ,Locus (genetics) ,Hemizygosity ,LIMK1 ,biology.organism_classification ,medicine.disease ,Biochemistry ,memory ,medicine ,Molecular Medicine ,Drosophila ,Drosophila melanogaster ,locomotor activity ,Molecular Biology ,Gene ,Research Article ,Biotechnology - Abstract
The molecular basis of the pathological processes that lead to genome disorders is similar both in invertebrates and mammals. Since cognitive impairments in Williams syndrome are caused by LIMK1 hemizy-gosity, could the spontaneous and mutant variants of the Drosophila limk1 gene serve as a model for studying two diagnostic features from three distinct cognitive defects of the syndrome? These two symptoms are the disturbance of visuospatial orientation and an unusualy strong fixation on the faces of other people during pairwise interaction with a stranger. An experimental approach to the first cognitive manifestation might be an analysis of the locomotor behavior of Drosophila larvae involving visuospatial orientation during the explora-tion of the surrounding environment. An approach to tackle the second manifestation might be an analysis of the most natural ways of contact between a male and a female during courtship (the first stage of this ritual is the orientation of a male towards a female and following the female with constant fixation on the female’s im-age). The present study of locomotor activity and cognitive repertoire in spontaneous and mutant variants of the Drosophila agnostic locus allows one to bridge alterations in the structure of the limk1 gene and behavior.KeyWordS Williams syndrome; LIMK1; Drosophila; locomotor activity; learning; memory.abbreViationS CRSC – conditioned reflex suppression of courtship; LI – learning index; CI – courtship index.introductionOver the past 20 years, Williams Syndrome has been re-garded as one of the most attractive models for estab-lishing a direct relationship between the genes, brain, and behavior [1, 2]. the syndrome results from a 1,500 kb deletion at 7q11.23, whose specific architecture predis-poses to unequal recombination. the deletion affects ap-proximately 20 genes; their hemizygosity manifests as a developmental anomaly characterized by cardiovascu-lar problems, “elfin” facial features, and several typical neurological anomalies and cognitive characteristics [3]. LIM-kinase 1 hemizygosity (LIMK1 is the key actin-re-modeling enzyme) causes cognitive impairments. they are characterized by a triad of signs: 1) a pronounced defect in visuospatial orientation; 2) a verbal linguistic defect of intermediate severity, which varies depending on the linguistic complexity of a certain culture; and 3) unusually strong gaze fixation on faces.experiments on higher animals are extremely ex-pensive; hence, simple animal models are needed to explore for and test drugs capable of correcting these disorders.can Drosophila melanogaster be used for this pur-pose? On the one hand, the functions of human disease genes are often identified from the way mutations manifest themselves in the Drosophila gene when its sequence is identical to that in the human gene. On the other hand, all the genes that reside in mammals in a single critical region being deleted in Williams syn-drome are known in Drosophila (let us remind read-ers that the frizzled-9 gene was first described in Drosophila). Despite the different evolutionary organi-zation of the Drosophila genome when these genes lo-calize on different chromosomes, the effect of a certain gene in the emergence of Williams syndrome can be analyzed if it meets the following criteria: 1) mutations of this gene must be known, while their hemizygosity would cause a mutant phenotype in Drosophila; 2) the architecture of the Drosophila gene locus may predis-pose to the emergence of chromosomal rearrangements due to unequal recombination; and 3) the gene locus must be characterized by increased recombination fre-quency, which may result in spontaneous generation of deletions or other rearrangements. this effect must
- Published
- 2014