ABSTRACT
During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey), and the segment selector, Ultrabithorax (Ubx), readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth), and/or the Zinc-finger protein, Teashirt (Tsh). In non-Hth/Tsh-expressing domains of these imaginal discs, however, gain of Ey in lgl− somatic clones induces neoplastic transformation in the distal wing disc and haltere, but not in the eye imaginal disc. Likewise, gain of Ubx in lgl− somatic clones induces transformation in the eye imaginal disc but not in its endogenous domain, namely, the haltere imaginal disc. Our results reveal that selector genes could behave as tumor drivers or inhibitors depending on the tissue contexts of their gains.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: R.P.G., A.B., P.S.; Methodology: R.P.G., A.B.; Formal analysis: R.P.G., A.B.; Investigation: R.P.G., A.B.; Writing - original draft: P.S.; Writing - review & editing: A.B.; Visualization: R.P.G., A.B., P.S.; Funding acquisition: P.S.
Funding
This work was supported by the Department of Biotechnology, Ministry of Science and Technology (DBT/PR14716/BRB/10/876/2011 to P.S.), the Wellcome Trust-DBT India Alliance (IA/E/13/1/501271 to A.B.), and the Council of Scientific and Industrial Research (Research Fellowship to R.P.G.).
Supplementary information
Supplementary information available online at http://bio.biologists.org/lookup/doi/10.1242/bio.027821.supplemental
- Received June 26, 2017.
- Accepted September 8, 2017.
- © 2017. Published by The Company of Biologists Ltd
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