4.6 Article

Drosophila MESR4 Gene Ensures Germline Stem Cell Differentiation by Promoting the Transcription of bag of marbles

Journal

CELLS
Volume 11, Issue 13, Pages -

Publisher

MDPI
DOI: 10.3390/cells11132056

Keywords

Drosophila; ovary; germline stem cell; stem cell niche; germ cell; stem cell differentiation; bag of marbles; MESR4

Categories

Funding

  1. Hungarian Scientific Research Fund (OTKA) [K132384, PD124446]
  2. National Research, Development, and Innovation Office [NKFIH-469-3/2020]
  3. Rollin D. Hotchkiss Foundation
  4. Janos Bolyai Fellowship

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It has been found that MESR4 is a transcription factor that promotes daughter cell differentiation in Drosophila ovarian stem cells. By promoting the transcription of key differentiation regulator gene bam, MESR4 regulates the decision-making and differentiation of ovarian stem cell daughter cells. Loss of MESR4 leads to the accumulation of daughter cells and differentiation defects.
Ovarian germline stem cells (GSCs) of Drosophila melanogaster provide a valuable in vivo model to investigate how the adult stem cell identity is maintained and the differentiation of the daughter cells is regulated. GSCs are embedded into a specialized cellular microenvironment, the so-called stem cell niche. Besides the complex signaling interactions between the germ cells and the niche cells, the germ cell intrinsic mechanisms, such as chromatin regulation and transcriptional control, are also crucial in the decision about self-renewal and differentiation. The key differentiation regulator gene is the bag of marbles (bam), which is transcriptionally repressed in the GSCs and de-repressed in the differentiating daughter cell. Here, we show that the transcription factor MESR4 functions in the germline to promote GSC daughter differentiation. We find that the loss of MESR4 results in the accumulation of GSC daughter cells which fail to transit from the pre-cystoblast (pre-CB) to the differentiated cystoblast (CB) stage. The forced expression of bam can rescue this differentiation defect. By a series of epistasis experiments and a transcriptional analysis, we demonstrate that MESR4 positively regulates the transcription of bam. Our results suggest that lack of repression alone is not sufficient, but MESR4-mediated transcriptional activation is also required for bam expression.

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