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  4. The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch

The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch

PNAS, 2010 · DOI: 10.1073/pnas.1005998107 · Published: October 26, 2010

UrologyGenetics

Simple Explanation

Cilia are important for how organs work and develop, but we don't know much about their role after an injury. This study looks at how cilia change when tissue is damaged or cysts form in the kidney. The researchers focused on a gene regulator called foxj1 that controls cilia-related genes. They discovered that one version of foxj1, called foxj1a, is quickly activated when cells are stretched, like when cysts grow in the kidney. This activation happens directly in response to the cell stretch, not because of other signals. The study also found that foxj1a is needed for cilia to move properly. When foxj1a is activated, it tells other genes to enhance cilia motility. This shows that cilia play a role in maintaining organ health after injury.

Study Duration
Not specified
Participants
Zebrafish embryos and adult zebrafish, murine cystic kidney disease models, and ischemia-reperfusion injury model
Evidence Level
Not specified

Key Findings

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    Zebrafish foxj1a, but not foxj1b, was rapidly induced in response to epithelial distension and stretch, kidney cyst formation, acute kidney injury, and crush injury in spinal cord cells.
  • 2
    Obstruction-induced up-regulation of foxj1a was not inhibited by cycloheximide, identifying foxj1a as a primary response gene to epithelial injury.
  • 3
    Enhanced foxj1a expression in obstructed tubules induced cilia motility target genes efhc1, tektin-1, and dnahc9.

Research Summary

The study investigates the role of cilia in injury and regeneration responses, focusing on the function of foxj1a, a transcriptional regulator of ciliagenes, in response to tissue damage and renal cyst formation. Results show that zebrafish foxj1a is rapidly induced in response to epithelial distension and stretch, kidney cyst formation, acute kidney injury, and crush injury in spinal cord cells, identifying it as a primary response gene to epithelial injury. The study demonstrates that foxj1a is specifically required for cilia motility and that enhanced foxj1a expression in obstructed tubules induces cilia motility target genes, revealing an essential role for foxj1 in modulating cilia function after injury.

Practical Implications

Understanding Ciliopathies

Provides insights into the molecular mechanisms underlying cystic kidney diseases and other ciliopathies, potentially leading to new therapeutic targets.

Regenerative Medicine

Suggests that modulating Foxj1 and downstream ciliogenic genes could be a novel therapeutic target to promote tissue repair in multiple forms of organ injury.

Diagnostic Marker

Foxj1 induction could serve as a diagnostic marker for early detection of tissue damage and injury.

Study Limitations

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