Selector genes display tumor cooperation and inhibition in Drosophila epithelium in a developmental context-dependent manner.

Ram Prakash Gupta,Pradip Sinha,Anjali Bajpai

doi:10.1242/bio.027821

Abstract

ABSTRACTDuring 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.

Highlights

IntroductionHierarchical order of expression of selector genes, which are broadly classified into segment-, fieldand cell fate-specific selectors (for review, see Akam, 1998; Mann and Carroll, 2002), regulate the specialization of individual body segments as well as those of the organs developing therein
During animal development, hierarchical order of expression of selector genes, which are broadly classified into segment, fieldand cell fate-specific selectors, regulate the specialization of individual body segments as well as those of the organs developing therein
The Vg field selector qualifies as a driver mutation in the margin cells of the eye disc. Such roles as tumor driver by Vg were observed in other developmental domains such as the leg epithelium, wherein lgl−UAS-vg clones underwent neoplastic transformation (Fig. S6C). These results reveal that selector genes can be a tumor driver in one developmental domain while being a passenger or a tumor inhibitor in another

Summary

Introduction

Hierarchical order of expression of selector genes, which are broadly classified into segment-, fieldand cell fate-specific selectors (for review, see Akam, 1998; Mann and Carroll, 2002), regulate the specialization of individual body segments as well as those of the organs developing therein. Misexpression of these selector genes, on the other hand, results in transdifferentiation (transdetermination) of one body part into another (Maves and Schubiger, 2003). Ectopic expression of the Vg and Ey field selectors, on the other hand, result in development of ectopic wings (Kim et al, 1996) and eyes (Halder et al, 1995), respectively

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