Drosophila twin spot clones reveal cell division dynamics in regenerating imaginal discs

Dept of Biology, University of Washington, Seattle WA 98195, USA.
Developmental Biology (Impact Factor: 3.55). 06/2011; 356(2):576-87. DOI: 10.1016/j.ydbio.2011.06.018
Source: PubMed


Cell proliferation is required for tissue regeneration, yet the dynamics of proliferation during regeneration are not well understood. Here we investigated the proliferation of eye and leg regeneration in fragments of Drosophila imaginal discs. Using twin spot clones, we followed the proliferation and fates of sister cells arising from the same mother cell in the regeneration blastema. We show that the mother cell gives rise to two sisters that participate equally in regeneration. However, when cells switch disc identity and transdetermine to another fate, they fail to turn off the cell cycle and continue dividing long after regeneration is complete. We further demonstrate that the regeneration blastema moves as a sweep of proliferation, in which cells are displaced. Our results suggest that regenerating cells stop dividing once the missing parts are formed, but if they undergo a switch in cell fate, the proliferation clock is reset.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The study of regeneration in Drosophila imaginal discs provides an opportunity to use powerful genetic tools to address fundamental problems pertaining to tissue regeneration and cell plasticity. We present a historical overview of the field and describe how the application of modern methods has made the study of disc regeneration amenable to genetic analysis. Discs respond to tissue damage in several ways: (a) Removal of part of the disc elicits localized cell proliferation and regeneration of the missing tissue. (b) Damage at specific locations in the disc can cause cells to generate disc-inappropriate structures (e.g., wing instead of leg), a phenomenon known as transdetermination. (c) Diffuse damage to imaginal discs, results in compensatory proliferation of surviving cells. Candidate-gene approaches have implicated the JNK, Wingless, and Hippo pathways in regeneration. Recently developed systems will enable extensive genetic screens that could provide new insights into tissue regeneration, transdetermination and compensatory proliferation. Expected final online publication date for the Annual Review of Genetics Volume 46 is November 02, 2012. Please see for revised estimates.
    No preview · Article · Aug 2012 · Annual Review of Genetics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the effect of methylation alteration in inflamed muscles from children with juvenile dermatomyositis (DM) and other idiopathic inflammatory myopathies (IIMs). Magnetic resonance imaging-directed diagnostic muscle biopsies yielded samples from 20 children with juvenile DM, which were used for genome-wide DNA methylation profiling, as were muscle biopsy samples from 4 healthy controls. Bisulfite treatment followed by pyrosequencing confirmed methylation status in juvenile DM and other IIMs. Immunohistochemistry defined localization and expression levels of WT1. Comparison of genome-wide DNA methylation profiling between juvenile DM muscle and normal control muscle revealed 27 genes with a significant methylation difference between the groups. These genes were enriched with transcription factors and/or cell cycle regulators and were unrelated to duration of untreated disease. Six homeobox genes were among them; ALX4, HOXC11, HOXD3, and HOXD4 were hypomethylated, while EMX2 and HOXB1 were hypermethylated. WT1 was significantly hypomethylated in juvenile DM (Δβ = -0.41, P < 0.001). Bisulfite pyrosequencing verification in samples from 56 patients with juvenile DM confirmed the methylation alterations of these genes. Similar methylation alterations were observed in juvenile polymyositis (n = 5) and other IIMs (n = 9). Concordant with the other findings, WT1 protein was increased in juvenile DM muscle, with average positive staining of 11.6%, but was undetectable in normal muscle (P < 0.001). These results suggest that affected muscles of children with juvenile DM and IIMs have the capacity to be repaired, and that homeobox and WT1 genes are epigenetically marked to facilitate this repair process, potentially suggesting new avenues of therapeutic intervention.
    Full-text · Article · Oct 2012 · Arthritis & Rheumatology
  • [Show abstract] [Hide abstract]
    ABSTRACT: During Drosophila development, the transcription factor Sp1 is necessary for proper leg growth and also to repress wing development. Here we test the role of Sp1 during imaginal disc regeneration. Ubiquitous expression of wg induces a regeneration blastema in the dorsal aspect of the leg disc. Within this outgrowth, the wing selector gene vg is activated in some cells, changing their fate to wing identity in a process known as transdetermination. In this report we demonstrate that reducing the gene copy number of Sp1 significantly increases both the frequency and the area of transdetermination in regenerating leg discs. By examining the expression of known Sp1 target genes, we also show that the proximo-distal patterning gene dachshund is downregulated dorsally, leading to a break in its normal ring-shaped expression pattern. We further report that transdetermination, as evidenced by Vg expression, is only observed when there is a broken ring of Dachshund expression. Combined, these studies establish a role for Sp1 in leg-to-wing transdetermination.
    No preview · Article · Nov 2012 · Developmental Biology
Show more