8/7/2023 0 Comments Mosaic shapes generator![]() ![]() ![]() In epithelia, sibling clones generally stay in close proximity. Mitotic descendants of the two original cells are generated, producing sibling clones (“twin spots”) when X segregation occurs (see text for details). Expression of FLP promotes recombination between the FRT sites specifically during the G2 phase of the cell cycle, generating two individual cells with distinct genotypes after the mitotic event. (A) trans-chromosomal recombination is mediated by the presence of FRT sites on distinct chromosomes. Trans-chromosomal and cis-chromosomal recombination. Their mobilization can lead to genomic diversity and heterogeneous cell populations ( van den Hurk et al. In addition, activation of mobile elements, such as the L1 retrotransposons that are transiently activated in preimplantation mammalian embryos, can lead to mosaicism. The ring-X chromosome is unstable and consequently is easily lost or broken during mitotic divisions, which promotes the formation of gynandromorphs ( Box 1). This defect can arise spontaneously or, more often, after induction of DNA damage by ionizing radiation ( Baker 1957). Mosaicism can also arise from ring-X chromosomes, where the two arms of the X chromosome have fused together to form a ring. Whether this has consequences for the animal depends upon the nature of the mutation and whether it is propagated. However, homologous recombination is not always a perfect process, and inaccurate repair can result in the formation of a genetic mosaic. In somatic cells, HDR relies on an identical sister chromatid, and thus is limited to G2 phase of the cell cycle ( Johnson and Jasin 2000). By contrast, HDR usually reestablishes the original sequence. ![]() 2004) in which the two broken DNA ends are joined without restoring the original sequence. NHEJ is a common repair mechanism in somatic cells ( Gloor et al. 2003) and Homology-Directed Repair (HDR). DSBs are repaired by two different cellular mechanisms: NHEJ (Nonhomologous End Joining) ( Moore and Haber 1996 Lieber et al. Mutations that give rise to mosaic tissues can originate from improperly repaired DNA double-strand breaks (DSBs) caused by environmental factors including ionizing radiation (UV light and X-ray) and a variety of chemicals, including nicotine ( Sachs et al. Mosaics can arise spontaneously from abnormal mitotic events and the persistence of the resulting mutant cell’s progeny, yielding a clone of mutant cells. We hope that our discussion will prompt readers to probe the literature for additional approaches, and perhaps spur the creation of new ways to use mosaic analysis in Drosophila research. While this review discusses many methods for generating mosaics, it is not exhaustive. In this chapter, our goal is to provide an overview of different ways in which genetic mosaics have been used and of some of the techniques that allow their generation. The experimental creation of genetic mosaics has permitted the study of essential genes, delineated cell lineages, helped distinguish between cell autonomous and nonautonomous gene function, and revealed how genetically distinct populations of cells can interact with each other. Mosaicism was harnessed as a research tool soon after Drosophila was established as a genetic model, and has since become indispensable for studies of the biology of development, physiology, and disease. Trisomy syndromes such as Turner and Klinefelter Syndromes also result from mosaicism, as do some milder forms of Down’s Syndrome ( Niikawa and Kajii 1984 De 2011). Cancers arise due to mosaicism, and the mosaic complexity of tumors can increase during their malignant progression. Mosaicism can be “silent” and cause no apparent harm to the individual ( Martincorena and Campbell 2015), but is also associated with numerous human pathologies. In nature, mosaics occur in all multicellular organisms and generally arise from a mutation within a single cell, acquired during development. Over the past century, the phenomenon of mosaicism has been extensively studied by geneticists and has become a vital tool in numerous aspects of biology. Genetic mosaics are individuals composed of cells with at least two different genotypes. ![]()
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