Genetic analysis of cadherin function in animal morphogenesis.

Cadherins are a superfamily of Ca(2+)-dependent adhesion molecules found in metazoans. Several classes of cadherins have been defined from which two - classic cadherins and Fat-like cadherins - have been studied by genetic approaches. Recent in vivo studies in Caenorhabditis elegans and Drosophila show that cadherins play an active role in a number of distinct morphogenetic processes. Classic cadherins function in epithelial polarization, epithelial sheet or tube fusion, cell migration, cell sorting, and axonal patterning. Fat-like cadherins are required for epithelial morphogenesis, proliferation control, and epithelial planar polarization.

The molecular evolution of development.

Morphological differences between species, from simple single-character differences to large-scale variation in body plans, can be traced to changes in the timing and location of developmental events. This has led to a growing interest in understanding the genetic basis behind the evolution of developmental systems. Molecular evolutionary genetics provides one of several approaches to dissecting the evolution of developmental systems, by allowing us to reconstruct the history of developmental genetic pathways, infer the origin and diversification of developmental gene functions, and assess the relative contributions of various evolutionary forces in shaping regulatory gene evolution.

Evolutionary aspects of primordial germ cell formation.

Animal embryos can be classified into three types depending on the time when the adult body form is specified--after metamorphosis, progressively by addition of posterior segments, or as a single event early in development. Segregation of germ cells correlates with specification of adult body form. When the adult body form is specified late in development, e.g. after metamorphosis (molluscs, echinoderms, cirripedes, hemichordates, cephalochordates and ascidians), germ cells appear in the early adult and at the site where the gonads will develop. When the adult body form is specified progressively during development by the sequential addition of posterior segments (annelids, onychophorans and most arthropods) germ cells are segregated either before or during addition of segments, in close association with the growth zone. In nematodes, chaetognaths, collembolans, higher holometabolous insects and vertebrates, the adult body form is specified early in development and germ cells are typically segregated correspondingly early and in extraembryonic regions. Therefore, as a general conclusion, germ cells appear to be segregated in locations and/or at times that exclude them from the process of specification of adult body form. Germ plasm is restricted to embryos in which exclusion of germ cells is difficult because the embryo is small or the signal specifying adult body form is pervasive. A possible role for germ plasm is thus as additional protection for the cells from the processes specifying adult body form.

All animals develop from a blastula: consequences of an undervalued definition for thinking on development.

An early embryo becomes a blastula at the moment that its constituent cells become organised into a simple epithelium. Epithelial folding and compartmentation are essential elements of animal development. All the different cell types--epithelial and other ones--of which a differentiated organism consists differ in their plasmamembrane-cytoskeletal complex but they are assumed to have an identical genome. The hypothesis is put forward that, perhaps, the basic mechanism underlying differentiation can be defined as the generation of cells which have an identical genome but which differ in their plasmamembrane-cytoskeletal complex and which, because of these differences, can engage in differential protein synthesis-physiology.

[Ontogenesis of animals from the position of absence of self-maintaining synthesis of regulatory proteins]. / Ontogenez zhivotnykh c pozitsii otsutsviia samopodderzhaniia sinteza reguliatornykh belkov.

The starting point of this paper is that there is no self-maintenance of most tissue-specific regulatory proteins. There in only one cycle within regulatory genes hierarchy--"germ line" cycle ensuring the next generation ontogeny. The consequences of this are stage-specificity of gene expression and organism ageing. To explain the existence of long-living differentiated cells, we assume that certain genes cause specific repression of mRNAs encoding regulatory proteins, thereby stabilizing the mRNAs. On the contrary, the mRNAs encoding regulatory proteins necessary for proliferation are to be translated due to growth factors. If one of the genes encoding such mRNAs acquires a foreign (viral, for example) promoter, the cell will divide infinitely; this can explain a number of nuclear proto-oncogenes properties. From this view-point, cell proliferation and differentiation, ontogeny and regeneration are considered.

Interspecific cell markers and lineage in mammals.

Study of cell lineage in the mammalian embryo has relied heavily on the use of chimeras to follow the fate of genetically marked cells in later development. Such studies have often been limited by the types of genetic markers available; there are very few markers that allow analysis of the spatial distribution of individual cells at all stages of development. We have developed a marker system that is based on the identification of cells of Mus musculus origin in M. musculus-M. caroli chimeras by in situ DNA-DNA hybridization using a cloned probe to M. musculus satellite DNA. This provides the first ubiquitous in situ cell marker system for mammalian chimeras. We have recently refined the system by the use of biotin-labelled probes and detection of hybridization by streptavidin-peroxidase binding. This increases both the speed and the resolution of the assay. We have used the marker for cell lineage analysis in both embryonic and adult chimeras and results from analysis of the derivatives of early cell lineages in later development and study of coherent growth versus cell mixing in the postimplantation embryo are presented. The importance of understanding embryonic cell lineages as a prelude to molecular studies is emphasized.