Investigating the influence of the transcription factor Hindsight in a Notch-induced tumour model

Abstract

In Drosophila development, the adult salivary gland and hindgut are derived from populations of undifferentiated cells that are found in the larval stages and are known as the salivary gland imaginal ring (SGIR) and hindgut imaginal ring (HIR). The SGIR and HIR have recently been developed as models for tumourigenesis. In these tissues, the Notch signaling pathway normally regulates proliferation, whereas overactivation results in severe overproliferation. Upon further investigation of this tumour model, cells located at the boundary of the SGIR, and its neighbouring differentiated larval cells have been characterized as a polyploid transition zone (TZ) that is a hotspot for metastatic transformation (Yang et al., 2019; Wang et al., 2021). We report here that the zinc finger transcription factor Hindsight is expressed in the TZ cells of the SGIR as well as the most anterior cells of the HIR. In both of these contexts, ectopic expression of hnt throughout the imaginal rings is sufficient to suppress cell proliferation and promote cell growth through the endocycle. Moreover, such ectopic expression of hnt is also sufficient to completely suppress Notch-induced overproliferation in both the SGIR and HIR. Analysis of hnt somatic mosaics within the SGIR suggests that Hnt can function to regulate proliferation in a cell non-autonomous manner. Co-expression of the cell cycle regulator string and hnt resulted in a rescue of the hnt overexpression phenotype, consistent with a role of hnt in the downregulation of the expression of string. Interestingly, the overexpression of hnt in both the SGIR and HIR frequently resulted in apparent deposition of melanin, suggesting hnt overexpression is capable of inducing trans-differentiation whereby undifferentiated cells adopt the fate of melanin-producing crystal cells.