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bioRxiv · 10.1101/615948

The gene brain tumor constrains growth to ensure proper patterning during regeneration in Drosophila imaginal discs

Abidi, S. N. F.·Smith-Bolton, R. K.
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Abstract

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 overgrowth 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. Author SummaryWhile much has been published about the signals that stimulate regeneration, the mechanisms that constrain and/or terminate regeneration have not been well characterized. Thus, we do not understand what limits may exist on the rate of regenerative growth, what mechanisms constrain regeneration, and what the consequences might be of enhancing regrowth. Here, we detail our discovery and characterization of a mechanism that constrains regeneration, and the deleterious effects of reducing that constraint. In this manuscript, we describe our identification of the RNA regulator Brat as a factor that constrains regenerative growth. Without this constraint on regenerative growth, patterning mistakes occur leading to a malformed regenerated structure. We demonstrate that the patterning errors are not due to faster growth itself, but are due to the overexpression of the pro-growth transcription factor Myc.

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Abidi, S. N. F., Smith-Bolton, R. K.. 2019-04-22. The gene brain tumor constrains growth to ensure proper patterning during regeneration in Drosophila imaginal discs. https://doi.org/10.1101/615948

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