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.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Germ granules in Drosophila

“…The tumor suppressor L(3)mbt was shown to secure somatic cellular identity in Drosophila ovaries and larval brains by repressing germline‐specific genes, including nanos. Given its well‐documented role in translational regulation, it is likely that the primary role of Nanos is to repress factors that promote somatic development rather than to actively promote germ cell development, akin to its recently reported role in C. elegans. Whether Nanos also has an independent role in actively promoting germ cell fate is less clear.…”

Generating and working with Drosophila cell cultures: Current challenges and opportunities

“…Not surprisingly, the molecular characteristics of Δmbt ‐OSC cells have been altered because of the modification. The cells phenocopied undifferentiated germ cells that accumulate in the mutant ovaries and ectopically express germline markers Aub, Vasa and AGO3 (Coux, Teixeira, & Lehmann, ; Ishizu et al, ; Saito et al, ; Sumiyoshi et al, ).…”

Investigations of HP1 and insulator partner protein 1 (HIPP1)

“…In line with this, pilot studies undertaken by Alexey Soshnev found that Rbp9, along with a number of other Su(Hw) repressed targets, becomes upregulated in a l(3)mbt temperature sensitive mutant line (SOSHNEV 2012). Similar to Su(Hw), loss of l(3)mbt specifically in the germline leads to increased egg chamber apoptosis (COUX et al 2018). Together, these studies suggest that L(3)mbt may be another candidate for facilitating Su(Hw) function.…”

“…Both complexes have been shown to repress developmental gene expression (GEORLETTE et al 2007;MEIER et al 2012). L(3)mbt, as part of the LINT complex, represses the expression of neuronal and testis specific genes in female germline cells (COUX et al 2018). Given the similarity of this function to that of Su(Hw) in the ovary (SOSHNEV et al 2013), L(3)mbt represents another candidate partner of Su(Hw) that might facilitate repression.…”