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1.  Sp1 modifies leg-to-wing transdetermination in Drosophila 
Developmental biology  2012;373(2):290-299.
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.
PMCID: PMC3557525  PMID: 23165292
Imaginal disc; regeneration; transdetermination; selector gene; dachshund
2.  Both Cyclin B levels and DNA-replication checkpoint control the early embryonic mitoses in Drosophila 
Development (Cambridge, England)  2003;131(2):10.1242/dev.00944.
The earliest embryonic mitoses in Drosophila, as in other animals except mammals, are viewed as synchronous and of equal duration. However, we observed that total cell-cycle length steadily increases after cycle 7, solely owing to the extension of interphase. Between cycle 7 and cycle 10, this extension is DNA-replication checkpoint independent, but correlates with the onset of Cyclin B oscillation. In addition, nuclei in the middle of embryos have longer metaphase and shorter anaphase than nuclei at the two polar regions. Interestingly, sister chromatids move faster in anaphase in the middle than the posterior region. These regional differences correlate with local differences in Cyclin B concentration. After cycle 10, interphase and total cycle duration of nuclei in the middle of the embryo are longer than at the poles. Because interphase also extends in checkpoint mutant (grapes) embryo after cycle 10, although less dramatic than wild-type embryos, interphase extension after cycle 10 is probably controlled by both Cyclin B limitation and the DNA-replication checkpoint.
PMCID: PMC3825093  PMID: 14681192
Early embryonic mitosis; Cdk1-CycB; Drosophila; Metaphase; Interphase
3.  Drosophila twin spot clones reveal cell division dynamics in regenerating imaginal discs 
Developmental biology  2011;356(2):576-587.
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.
PMCID: PMC3144724  PMID: 21722631
regeneration; transdetermination; cell cycle; somatic cell immortality
Developmental biology  2010;347(2):315-324.
Imaginal discs of Drosophila have the remarkable ability to regenerate. After fragmentation wound healing occurs, ectopic wg is induced and a blastema is formed. In some, but not all fragments, the blastema will replace missing structures and a few cells can become more plastic and transdetermine to structures of other discs. A series of systematic cuts through the first leg disc revealed that a cut must transect the dorsal-proximal disc area and that the fragment must also include wg-competent cells. Fragments that fail to both transdetermine and regenerate missing structures will do both when provided with exogenous Wg, demonstrating the necessity of Wg in regenerative processes. In intact leg discs ubiquitously expressed low levels of Wg also leads to blastema formation, regeneration and transdetermination. Two days after exogenous wg induction the endogenous gene is activated, leading to elevated levels of Wg in the dorsal aspect of the leg disc. We identified a wg enhancer that regulates ectopic wg expression. Deletion of this enhancer increases transdetermination, but lowers the amount of ectopic Wg. We speculate that this lessens repression of dpp dorsally, and thus creates a permissive condition under which the balance of ectopic Wg and Dpp is favorable for transdetermination.
PMCID: PMC2976676  PMID: 20816798
5.  The Twin Spot Generator for differential Drosophila lineage analysis 
Nature methods  2009;6(8):600-602.
In Drosophila, widely-used mitotic recombination-based strategies generate mosaic flies with positive readout for only one daughter cell after division. To differentially label both daughter cells, we developed the Twin Spot Generator technique (TSG) and demonstrate that through mitotic recombination, TSG generates green and red twin spots in internal fly tissues, visible even as single cells. We discuss the wide applications of TSG to lineage and genetic mosaic studies.
PMCID: PMC2720837  PMID: 19633664
6.  Three genes control the timing, the site and the size of blastema formation in Drosophila 
Developmental biology  2008;319(1):68-77.
Regeneration is a vital process to maintain and repair tissues. Despite the importance of regeneration, the genes responsible for regenerative growth remain largely unknown. In Drosophila, imaginal disc regeneration can be induced either by fragmentation and in vivo culture or in situ by ubiquitous expression of wingless (wg/wnt1). Imaginal discs, like appendages in lower vertebrates, initiate regeneration by wound healing and proliferation at the wound site, forming a regeneration blastema. Most blastema cells maintain their disc-specific identity during regeneration; a few cells however, exhibit stem-cell like properties and switch to a different fate, in a phenomenon known as transdetermination. We identified three genes, regeneration (rgn), augmenter of liver regeneration (alr) and Matrix metalloproteinase-1 (Mmp1) expressed specifically in blastema cells during disc regeneration. Mutations in these genes affect both fragmentation- and wg-induced regeneration by either delaying, reducing or positioning the regeneration blastema. In addition to the modifications of blastema homeostasis, mutations in the three genes alter the rate of regeneration-induced transdetermination. We propose that these genes function in regenerative proliferation, growth and regulate cellular plasticity.
PMCID: PMC2483308  PMID: 18485344
7.  A screen for genes that function in leg disc regeneration in Drosophila melanogaster 
Mechanisms of development  2007;125(1-2):67-80.
Many diverse animal species regenerate parts of an organ or tissue after injury. However, the molecules responsible for the regenerative growth remain largely unknown. The screen reported here aimed to identify genes that function in regeneration and the transdetermination events closely associated with imaginal disc regeneration using Drosophila melanogaster. We screened a collection of 97 recessive lethal P-lacZ enhancer trap lines for two primary criteria: first, the ability to dominantly modify wg-induced leg-to-wing transdetermination and second, for the activation or repression of the lacZ reporter gene in the blastema during disc regeneration. Of the 97 P-lacZ lines, we identified six genes (Kr├╝ppelhomolog- 1, rpd3, jing, combgap, Aly and S6 kinase) that met both criteria. Five of these genes suppress, while one enhances, leg-to-wing transdetermination and therefore affects disc regeneration. Two of the genes, jing and rpd3, function in concert with chromatin remodeling proteins of the Polycomb Group (PcG) and trithorax Group (trxG) genes during Drosophila development, thus linking chromatin remodeling with the process of regeneration.
PMCID: PMC2225348  PMID: 18036784
Drosophila; Imaginal discs; Regeneration; Transdetermination; Wingless; Blastema; Chromatin remodeling; Enhancer trap; P-elements; Genetic screen
8.  Transdetermination: Drosophila imaginal disc cells exhibit stem cell-like potency 
Drosophila imaginal discs, the primordia of the adult fly appendages, are an excellent system for studying developmental plasticity. Cells in the imaginal discs are determined for their disc-specific fate (wingness, legness) during embryogenesis. Disc cells maintain their determination during larval development, a time of extensive growth and proliferation. Only when prompted to regenerate do disc cells exhibit lability in their determined identity. Regeneration in the disc is mediated by a localized region of cell division, known as the regeneration blastema. Most regenerating disc cells strictly adhere to their disc-specific identity; some cells however, switch fate in a phenomenon known as transdetermination. Similar regeneration and transdetermination events can be induced in situ by misexpression of the signaling molecule wingless. Recent studies indicate that the plasticity of disc cells during regeneration is associated with high morphogen activity and the reorganization of chromatin structure. Here we provide both a historical perspective of imaginal disc transdetermination, as well as discuss recent findings on how imaginal disc cells acquire developmental plasticity and multipotency. We also highlight how an understanding of imaginal disc transdetermination can enhance an understanding of developmental potency exhibited by stem cells.
PMCID: PMC2000801  PMID: 17317270
Drosophila; transdetermination; imaginal disc; stem cell; potency

Results 1-8 (8)