L(3)mbt and the LINT complex safeguard tissue identity in the Drosophila ovary

Abstract

Maintenance of cellular identity is essential for tissue development and homeostasis. At the molecular level, cell identity is determined by the coordinated activation and repression of defined sets of genes. Defects in the maintenance of the genetic programs required for identity can have dire consequences such as organ malformation and cancer. The tumor suppressor L(3)mbt was shown to secure cellular identity in Drosophila larval brains by repressing germline-specific genes. Here we interrogate the temporal and spatial requirements for L(3)mbt in the Drosophila ovary, and show that it safeguards the integrity of both somatic and germline tissues. L(3)mbt mutant ovaries exhibit multiple developmental defects, which we find to be largely caused by the inappropriate expression of a single gene, nanos, a key regulator of germline fate, in the somatic cells of the ovary. In the female germline, we find that L(3)mbt represses testis-specific and neuronal genes. Molecularly, we show that L(3)mbt function in the ovary is mediated through its cofactor Lint1 but independent of the dREAM complex. Together, our work uncovers a more complex role for L(3)mbt than previously understood and demonstrates that L(3)mbt secures tissue identity by preventing the simultaneous expression of original identity markers and tissue-specific misexpression signatures.