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Analysis of Nephron Composition and Function in the Adult Zebrafish Kidney
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The absence of Trim28 in nephron progenitors results in impaired kidney development and function

Balazs Palhazi1, Alireza Paikari1, Greta Clarén1

  • 1Department of Developmental Biochemistry, Theodor Boveri-Institute, University of Würzburg, D-97074 Würzburg, Germany.

Development (Cambridge, England)
|July 29, 2026
PubMed

Insights

The transcriptional regulator TRIM28 (tripartite motif-containing protein 28) is crucial for kidney development. Its deletion impairs nephron progenitor cells and proximal tubule formation in mice.

Area of Science:

  • Developmental Biology
  • Genetics
  • Oncology

Background:

  • The TRIM28 gene encodes a transcriptional regulator involved in diverse molecular processes.
  • TRIM28 inactivation is linked to Wilms tumor, a pediatric renal malignancy, suggesting a role in kidney development.

Purpose of the Study:

  • To investigate the role of TRIM28 in kidney morphogenesis and nephrogenesis.
  • To analyze the impact of TRIM28 deletion on kidney development using a conditional knockout mouse model.

Main Methods:

  • Generated Trim28 conditional knockout (Trim28Δ/Δ) mice by deleting Trim28 in nephron progenitors.
  • Performed transcriptome and single-cell RNA sequencing (scRNA-seq) analyses on Trim28Δ/Δ kidneys.
  • Examined kidney weight, renal structure, and cell-type composition.

Main Results:

  • Trim28 deletion led to early postnatal lethality and reduced kidney weight in mice.
  • Proximal tubules (PTs) were disorganized, with decreased nephron progenitor cells (NPCs) and increased PT cells.
  • Deregulation of retroelement expression and a shift towards inflammatory gene expression patterns were observed.

Conclusions:

  • TRIM28 is essential for the maintenance and differentiation of NPCs and PT cells during kidney development.
  • While not causing tumors in this model, TRIM28 deficiency impacts progenitor cell function, showing similarities to TRIM28 mutant tumor cells.
  • TRIM28 plays a critical role in early kidney morphogenesis and cellular homeostasis.
Keywords:
Trim28Kidney developmentKidney tubule functionMouseSingle-cell sequencingTransposable elements

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