[Systemic regulation of genetic and cytogenetic processes by a signal cascade of actin remodeling: locus agnostic in Drosophila].

The concept on systemic regulation of genetic and cytogenetic processes has acquired a new perspective after the completion of the Human Genome project, when the view on systemic realization of genetic activity in the dynamic spatial organization of the genome is the nucleus was generally accepted. This organization underlies plasticity of complex biological systems. Chromosome position within the nucleus determined both processes of normal development and the development of genomic diseases, i.e., changes according to the environmental requirements, current needs of the organism, and its individual experience. Nuclear actin has been envisioned as a main factor bridging three levels of the genome organization (nucleotide, structural, and spatial), due to its capability of (1) regulating transcription by activating all three classes of RNA polymerase; (2) participating in chromatin remodeling by interacting with numerous proteins; and (3) lining the nuclear membrane, determining the chromosome attachment points and regulating export from the nucleus. In view of this, the role of actin remodeling factors (LIMK1, cofilin, actin) in the development of neurodegenerative diseases, including prionic ones, and in the mechanisms of generation of genomic diseases, syndromes resulting from unequal recombination, has been intensely studied. Drosophila is a helpful model organism to determine the sequence of events in this system of hierarchical relationships. Using spontaneous and mutant variants of the agnostic locus, we have designed a model of the Williams syndrome, which also reproduces main diagnostic traits of neurodegenerative diseases.