Abstract
Regeneration following tissue damage often necessitates a mechanism for cellular re-programming, so that surviving cells can give rise to all cell types originally found in the damaged tissue. This process, if unchecked, can also generate cell types that are inappropriate for a given location. We conducted a screen for genes that negatively regulate the frequency of notum-to-wing transformations following genetic ablation and regeneration of the wing pouch, from which we identified mutations in the transcriptional co-repressor C-terminal Binding Protein (CtBP). When CtBP function is reduced, ablation of the pouch can activate the JNK/AP-1 and JAK/STAT pathways in the notum to destabilize cell fates. Ectopic expression of Wingless and Dilp8 precede the formation of the ectopic pouch, which is subsequently generated by recruitment of both anterior and posterior cells near the compartment boundary. Thus, CtBP stabilizes cell fates following damage by opposing the destabilizing effects of the JNK/AP-1 and JAK/STAT pathways.
Highlights
As development proceeds in multicellular organisms, cells become more restricted in developmental potential
We identified mutations in the gene encoding the transcriptional co-repressor, C-terminal Binding Protein (CtBP), and show that CtBP opposes the destabilization of cell fates during regeneration caused by JNK and the JAK/STAT pathway
To investigate what was triggering the formation of ectopic wings (EW), we focused on the early stages of ectopic pouch formation
Summary
As development proceeds in multicellular organisms, cells become more restricted in developmental potential This results initially from the expression of lineage-specific transcription factors and is stabilized by heritable chromatin states that restrict accessibility of the transcriptional machinery to subsets of genes (Britten and Davidson, 1969; Levine, 2010; Allis and Jenuwein, 2016). Groups of cells at particular locations are specified to form particular imaginal discs (e.g. genital disc, wing disc, eye-antennal disc) depending on their location in the embryo (Cohen, 1993) These fates are determined during embryogenesis, disc cells do not differentiate to form adult structures until many days later, when metamorphosis occurs.
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