Regenerative growth is constrained by brain tumor to ensure proper patterning in Drosophila.

Some animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent aberrant growth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure.

Cell fate changes induced by a Distal-less enhancer-trap transgene in the Drosophila antennal imaginal disc.

The imaginal discs of the genetically tractable model organism Drosophila melanogaster have been used to study cell-fate specification and plasticity, including homeotic changes and regeneration-induced transdetermination. The identity of the reprogramming mechanisms that induce plasticity has been of great interest in the field. Here we identify a change from antennal fate to eye fate induced by a Distal-less-GAL4 (DllGAL4) P-element insertion that is a mutant allele of Dll and expresses GAL4 in the antennal imaginal disc. While this fate change is not induced by tissue damage, it appears to be a hybrid of transdetermination and homeosis as the GAL4 expression causes upregulation of Wingless, and the Dll mutation is required for the fate change. Neither GAL4 expression nor a Dll mutation on its own is able to induce antenna-to-eye fate changes. This plasticity appears to be unique to the DllGAL4 line, possibly due to cellular stress induced by the high GAL4 expression combined with the severity of the Dll mutation. Thus, we propose that even in the absence of tissue damage, other forms of cellular stress caused by high GAL4 expression can induce determined cell fates to change, and selector gene mutations can sensitize the tissue to these transformations.

Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc.

The study of regeneration would be aided greatly by systems that support large-scale genetic screens. Here we describe a nonsurgical method for inducing tissue damage and regeneration in Drosophila larvae by inducing apoptosis in the wing imaginal disc in a spatially and temporally regulated manner. Tissue damage results in localized regenerative proliferation characterized by altered expression of patterning genes and growth regulators as well as a temporary loss of markers of cell fate commitment. Wingless and Myc are induced by tissue damage and are important for regenerative growth. Furthermore, ectopic Myc enhances regeneration when other growth drivers tested do not. As the animal matures, the ability to regenerate is lost and cannot be restored by activation of Wingless or Myc. This system is conducive to forward genetic screens, enabling an unbiased search for genes that regulate both the extent of and the capacity for regeneration.