Abstract
ABSTRACTMaintenance 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. The tumor suppressor L(3)mbt has been 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 ovarian cells. In the female germline, we find that L(3)mbt represses testis-specific and neuronal genes. At the molecular level, we show that L(3)mbt function in the ovary is mediated through its co-factor Lint-1 but independently 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.
Highlights
Development requires tight control of gene expression as differentiating cells must express lineage-specific genes while repressing genes that promote other fates
Sterility in l(3)mbt mutant females is associated with aberrant ovarian development L(3)mbt was previously shown to be required for the development of the nervous system as l(3)mbt mutant flies grown at restrictive temperatures (29 ̊C) develop malignant brain tumors and die at larval stages (Gateff et al, 1993; Janic et al, 2010; Richter et al, 2011)
L(3)mbt depletion does not result in complete transdifferentiation but causes simultaneous expression of original cell signatures and ectopic expression of markers of other cell fates
Summary
Development requires tight control of gene expression as differentiating cells must express lineage-specific genes while repressing genes that promote other fates. Gene expression profiling of l(3)mbt brain tumors and L(3)mbt-depleted cultured somatic cells identified a group of upregulated genes known as the Malignant Brain Tumor Signature (MBTS) that is enriched for factors expressed in germ cells (Georlette et al, 2007; Janic et al, 2010; Meier et al, 2012; Sumiyoshi et al, 2016). Our lab showed that strong l(3)mbt mutations cause a maternal, germline autonomous phenotype that precludes normal embryonic development including primordial germ cell formation (Yohn et al., 2003). Together, these studies suggest that L(3)mbt may impart many functions in regulation of tissue identity
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