# TrxT and dhd are dispensable for Drosophila brain development but essential for l(3)mbt brain tumour growth

## TL;DR

The genes TrxT and dhd are not needed for normal brain development in fruit flies but are essential for the growth of certain brain tumors.

## Contribution

This study identifies the first X-linked, head-to-head cancer-germline gene pair in Drosophila with a role in tumor growth.

## Key findings

- TrxT and dhd are not expressed during normal brain development.
- TrxT and dhd synergistically drive l(3)mbt tumor transcriptomic signatures and growth.
- TrxT is crucial for long-term allografted tumor growth, but dhd is not.

## Abstract

Expression of the Drosophila cancer-germline (CG), X-linked, head-to-head gene pair TrxT and dhd is normally germline-specific but becomes upregulated in brain tumours caused by mutation in l(3)mbt. Here, we show that TrxT and dhd play a major synergistic role in the emergence of l(3)mbt tumour-linked transcriptomic signatures and tumour development, which is remarkable, taking into account that these two genes are never expressed together under normal conditions. We also show that TrxT, but not dhd, is crucial for the growth of l(3)mbt allografts, hence suggesting that the initial stages of tumour development and long-term tumour growth may depend on different molecular pathways. In humans, head-to-head inverted gene pairs are abundant among CG genes that map to the X chromosome. Our results identify a first example of an X-linked, head-to-head CG gene pair in Drosophila, underpinning the potential of such CG genes, dispensable for normal development and homoeostasis of somatic tissue, as targets to curtail malignant growth with minimal impact on overall health.

The Drosophila cancer-germline, head-to-head gene pair TrxT and dhd is dispensable for normal brain development but plays a major role in the expression of mbt tumour transcriptomic signatures and neoplastic growth.

Germline specific thioredoxins TrxT and dhd are dispensable for larval brain development.TrxT and dhd synergistically contribute to mbt larval brain tumour growth.TrxT, but not dhd, is crucial for long-term growth of allografted mbt tumours.TrxT and dhd underpin the potential of cancer-germline genes as ideal targets to curtail malignant growth.

Germline specific thioredoxins TrxT and dhd are dispensable for larval brain development.

TrxT and dhd synergistically contribute to mbt larval brain tumour growth.

TrxT, but not dhd, is crucial for long-term growth of allografted mbt tumours.

TrxT and dhd underpin the potential of cancer-germline genes as ideal targets to curtail malignant growth.

The Drosophila cancer-germline, head-to-head gene pair TrxT and dhd is dispensable for normal brain development but plays a major role in the expression of mbt tumour transcriptomic signatures and neoplastic growth.