Regulation of cellular plasticity inDrosophilaimaginal disc cells by the Polycomb group, trithorax group andlamagenes

Abstract

Drosophila imaginal disc cells can switch fates by transdetermining from one determined state to another. We analyzed the expression profiles of cells induced by ectopic Wingless expression to transdetermine from leg to wing by dissecting transdetermined cells and hybridizing probes generated by linear RNA amplification to DNA microarrays. Changes in expression levels implicated a number of genes: lamina ancestor, CG12534 (a gene orthologous to mouse augmenter of liver regeneration), Notch pathway members, and the Polycomb and trithorax groups of chromatin regulators. Functional tests revealed that transdetermination was significantly affected in mutants for lama and seven different PcG and trxG genes. These results validate our methods for expression profiling as a way to analyze developmental programs, and show that modifications to chromatin structure are key to changes in cell fate. Our findings are likely to be relevant to the mechanisms that lead to disease when homologs of Wingless are expressed at abnormal levels and to the manifestation of pluripotency of stem cells.

Transdetermination: Drosophila imaginal disc cells exhibit stem cell-like potency

“…lama encodes a novel protein that is expressed in glial and neuronal precursor cells in the Drosophila lamina prior to differentiation (Perez & Steller, 1996). A similar pattern of lama expression is observed in developing leg discs, with expression observed in early but not late third instar leg discs (Klebes et al, 2005). The reactivation of lama expression in TD leg cells suggests that lama might prevent differentiation, a potential step required for acquiring disc cell multipotency.…”

“…The frequency of TD is lowered in a JNK heterozygote mutant background, indicating that down-regulation of PcG repression is necessary for the cell fate switches. Similarly, Klebes et al (2005) found that upon ubiquitous wg signaling the expression levels of 15 of the 32 PcG and trxG genes were specifically altered in vg-expressing leg disc cells. Heterozygous mutations in several of these genes (Polycomb, Enhancer of zeste, Enhancer of polycomb, Sex comb on midleg, Su(z)2, brahma and osa) dominantly modified the frequency and area of wg-induced leg-to-wing TD (Klebes et al, 2005;Lee, Maurange, Ringrose, & Paro, 2005).…”

“…Similarly, Klebes et al (2005) found that upon ubiquitous wg signaling the expression levels of 15 of the 32 PcG and trxG genes were specifically altered in vg-expressing leg disc cells. Heterozygous mutations in several of these genes (Polycomb, Enhancer of zeste, Enhancer of polycomb, Sex comb on midleg, Su(z)2, brahma and osa) dominantly modified the frequency and area of wg-induced leg-to-wing TD (Klebes et al, 2005;Lee, Maurange, Ringrose, & Paro, 2005). These observations indicate that modulation of PcC/trxG proteins, specifically in regenerating disc cells, may facilitate a switch in fate, possibly by changing the transcriptional accessibility of chromatin to a more reprogrammable state.…”

“…New insight into putative downstream genes that initiate and elaborate TD comes from analyzing the transcriptional profile of leg disc cells that TD to wing following ectopic wg expression (Klebes et al, 2005). Using microarray, approximately 140 'TD' genes were identified whose expression levels were enriched in vg-expressing leg cells (Klebes et al, 2005).…”

“…Using microarray, approximately 140 'TD' genes were identified whose expression levels were enriched in vg-expressing leg cells (Klebes et al, 2005). Interestingly, many candidate 'TD' genes are known to suppress differentiation.…”