Novel regulators of zebrafish glomerular development

CRISPR-Cas9 G0 mutagenesis in 3-day-post-fertilization zebrafish pronephric glomeruli identified eight genes whose disruption is linked to glomerular proteinuria.

• Why it matters: Many susceptibility genes for filtration defects are known, but additional pathways likely remain undiscovered, limiting understanding of glomerular cell differentiation and function.
• What they did: The team built a glomerulus-enriched larval zebrafish transcriptome and then screened twelve less-characterized, glomerulus-enriched genes using CRISPR-Cas9, measuring leakage of rhodamine-labeled 500 kDa dextran.
• The result: Eight genes emerged as potential new proteinuria causes, including regulators of small GTPases (fam49ba/cyrib, rasgrp3), ptprq, and frmd6, enabling targeted follow-up of glomerular development pathways.

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