ETS transcription factors regulate precise matrix metalloproteinase expression and follicle rupture in Drosophila

Development. 2024 Mar 1;151(5):dev202276. doi: 10.1242/dev.202276. Epub 2024 Feb 28.

Abstract

Drosophila matrix metalloproteinase 2 (MMP2) is specifically expressed in posterior follicle cells of stage-14 egg chambers (mature follicles) and is crucial for the breakdown of the follicular wall during ovulation, a process that is highly conserved from flies to mammals. The factors that regulate spatiotemporal expression of MMP2 in follicle cells remain unknown. Here, we demonstrate crucial roles for the ETS-family transcriptional activator Pointed (Pnt) and its endogenous repressor Yan in the regulation of MMP2 expression. We found that Pnt is expressed in posterior follicle cells and overlaps with MMP2 expression in mature follicles. Genetic analysis demonstrated that pnt is both required and sufficient for MMP2 expression in follicle cells. In addition, Yan was temporally upregulated in stage-13 follicle cells to fine-tune Pnt activity and MMP2 expression. Furthermore, we identified a 1.1 kb core enhancer that is responsible for the spatiotemporal expression of MMP2 and contains multiple pnt/yan binding motifs. Mutation of pnt/yan binding sites significantly impaired the Mmp2 enhancer activity. Our data reveal a mechanism of transcriptional regulation of Mmp2 expression in Drosophila ovulation, which could be conserved in other biological systems.

Keywords: ETS-family transcription factors; Enhancer; MMP2; Ovulation; Pointed; Yan.

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila* / metabolism
  • Female
  • Mammals / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Nerve Tissue Proteins / metabolism
  • Ovulation / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / metabolism
  • Signal Transduction / physiology
  • Transcription Factors / genetics

Substances

  • Matrix Metalloproteinase 2
  • Proto-Oncogene Proteins c-ets
  • DNA-Binding Proteins
  • Drosophila Proteins
  • pnt protein, Drosophila
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors