[Evolutionary Stability of Gene Regulatory Networks That Define the Temporal Identity of Neuroblasts].

The ensemble of gap genes is one of the best studied and most conserved gene regulatory networks (GRNs). Gap genes, such as hunchback (hb), Krüppel (Kr), pou-domain (pdm; pdm1 and pdm2), and castor (cas) genes belong to the well-known families Ikaros (IKZF1/hb), Krüppel-like factor (KLF/Kr), POU domain (BRN1/pdm-1, BRN2/pdm-2), and Castor homologs (CASZ1/cas), which are present in all vertebrate genomes and code for site-specific transcription factors. Gap genes form a core of an embryonic segmentation control subnetwork and define the temporal identity of neuroblasts in Drosophila embryos. The key gene regulatory mechanisms whereby the gap genes govern segmentation and neurogenesis are similar. Moreover, the gap genes are evolutionarily conserved in terms of their function as a core of the temporal specification GRN during neurogenesis in vertebrates, including humans. A problem of special interest is to understand the extent of conservation for the molecular mechanisms involved in the regulatory functions of the gap genes. The problem is especially important because human orthologs of the gap gens are crucial for many pathophysiological processes, including tumor growth suppression.

Evolutionary Design of Gene Networks: Forced Evolution by Genomic Parasites.

The co-evolution of species with their genomic parasites (transposons) is thought to be one of the primary ways of rewiring gene regulatory networks (GRNs). We develop a framework for conducting evolutionary computations (EC) using the transposon mechanism. We find that the selective pressure of transposons can speed evolutionary searches for solutions and lead to outgrowth of GRNs (through co-option of new genes to acquire insensitivity to the attacking transposons). We test the approach by finding GRNs which can solve a fundamental problem in developmental biology: how GRNs in early embryo development can robustly read maternal signaling gradients, despite continued attacks on the genome by transposons. We observed co-evolutionary oscillations in the abundance of particular GRNs and their transposons, reminiscent of predator-prey or host-parasite dynamics.

HOX Pro: a specialized database for clusters and networks of homeobox genes.

It is now clear that the homeobox motif is well conserved across metazoan phyla. It has been established experimentally that a subset of genes containing this motif plays key roles in the orchestration of gene expression during development. Auto- and cross-regulatory functional interactions join homeobox genes into genetic networks. We have developed a specialized database HOX-Pro in order to arrange all available data on structure, function, phylogeny and evolution of Hox genes, Hox clusters and Hox networks. Its primary location is http://www.iephb.nw.ru/hoxpro. The database is also mirrored at http://www.mssm.edu/molbio/hoxpro. The HOX-Pro database is aimed at: (i) analysis and classification of regulatory and coding regions in diverse homeobox and related genes; (ii) comparative analysis of organization of 'Hox-based' genetic networks in the sea urchin Strongylocentrotus purpuratus, the fruit fly Drosophila melanogaster and the mouse Mus musculus; and (iii) analysis of phylogeny and evolution of homeobox genes and clusters.

Graphical interface to the genetic network database GeNet.

UNLABELLED: We designed a Java applet which enables the visualization of genetic networks and can be used as a Web publishing tool by molecular biologists studying the mechanisms of gene interactions. AVAILABILITY: http://www. csa.ru/Inst/gorb_dep/inbios/ genet/Graph/Genes_Graph.html CONTACT: samson@fn.csa.ru

[The role of conserved sequences in the regulatory elements of the Antp-like homeobox-containing genes of vertebrates]. / Rol' nekotorykh konservativnykh posledovatel'nostei v reguliatornykh élementakh Antp-podobnykh gomeobokssoderzhashchikh genov pozvonochnykh.

By the present time the homeobox genes have been found in the representatives of the main invertebrate and vertebrate taxa. It has been demonstrated that these genes play the key role in the space and time genome expression orchestration in ontogenesis. The autoregulatory and cross-regulatory functional interactions integrate the homeobox genes into the gene networks. We found a correlation in variability of the coding and regulatory regions for vertebrate homeobox genes. The phylogenetic relations of structure and regulatory elements involved into the cross- and autoregulatory connections have been investigated in detail. The comprehensive phylogenetic analysis of the promoter region for these genes compared to results of such analysis of their homeoboxes has revealed two opposed tendencies in evolution of the regulatory elements of genes. The first trend is conservation of many regulatory elements in evolution of vertebrate homeobox genes and the second one is high variability of other non-coding gene regions.

[The pattern of the expression of homeo box-containing genes in the mesenchyme of the mammalian limb bud as a coordinate network for subsequent morphogenetic processes]. / Pattern ékspressii gomeobokssoderzhashchikh genov v mezenkhime pochki konechnosti mlekopitaiushchego kak koordinatnaia set' dlia posleduiushchikh morfogeneticheskikh protsessov.

Hypothesis is developed about mechanisms of determination of limb bud of mammals as a result of expression of homeo box containing genes (hox genes) of known up to date four hox families. Spatial pattern of the expression plays a role of coordinate system for subsequent processes of morphogenesis and differentiation of the limbs. Propositions of the hypothesis are realized in a computer dynamic model. The results of modeling are compared with known data on features of the expression of hox genes in the mesenchyme of developing limb buds in mammals and birds.