ArticleJournal of the American Society of Nephrology : JASN2014
Lmx1b and FoxC combinatorially regulate podocin expression in podocytes.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- FOXC2 and WT1 regulate transcriptional reprogramming during the podocyte response to injury.JCI insight · 2026Article
- Article
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- Characterisation of lmx1b paralogues in zebrafish reveals divergent roles in skeletal, kidney and muscle development.Biology open · 2025Article
- A statistical framework for inferring genetic requirements from embryo-scale single-cell sequencing experiments.bioRxiv : the preprint server for biology · 2025Article
- Epigenomic regulation of stemness contributes to the low immunogenicity of the most mutated human cancer.Cell reports · 2025Article
- Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish.Journal of developmental biology · 2023Review
- Alteration in DNA-binding affinity of Wilms tumor 1 protein due to WT1 genetic variants associated with steroid - resistant nephrotic syndrome in children.Scientific reports · 2022Article
- Transgenic fluorescent zebrafish lines that have revolutionized biomedical research.Laboratory animal research · 2021Review
- Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature Podocytes.Journal of the American Society of Nephrology : JASN · 2021Article
- Epigenetic transcriptional reprogramming by WT1 mediates a repair response during podocyte injury.Science advances · 2020Article
- Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats.Scientific reports · 2020Article
- Review
- Proteinuric Kidney Diseases: A Podocyte's Slit Diaphragm and Cytoskeleton Approach.Frontiers in medicine · 2018Review
- Inducible ATF3-NFAT axis aggravates podocyte injury.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy.Pediatric nephrology (Berlin, Germany) · 2017Review
- The zebrafish kidney mutant zeppelin reveals that brca2/fancd1 is essential for pronephros development.Developmental biology · 2017Article
- Nephron number, hypertension, and CKD: physiological and genetic insight from humans and animal models.Physiological genomics · 2017Review
- A Drosophila model system to assess the function of human monogenic podocyte mutations that cause nephrotic syndrome.Human molecular genetics · 2017Article
- Podocyte-actin dynamics in health and disease.Nature reviews. Nephrology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
Podocin is a key protein of the kidney podocyte slit diaphragm protein complex, an important part of the glomerular filtration barrier. Mutations in the human podocin gene NPHS2 cause familial or sporadic forms of renal disease owing to the disruption of filtration barrier integrity. The exclusive expression of NPHS2 in podocytes reflects its unique function and raises interesting questions about its transcriptional regulation. Here, we further define a 2.5-kb zebrafish nphs2 promoter fragment previously described and identify a 49-bp podocyte-specific transcriptional enhancer using Tol2-mediated G0 transgenesis in zebrafish. Within this enhancer, we identified a cis-acting element composed of two adjacent DNA-binding sites (FLAT-E and forkhead) bound by transcription factors Lmx1b and FoxC. In zebrafish, double knockdown of Lmx1b and FoxC orthologs using morpholino doses that caused no or minimal phenotypic changes upon individual knockdown completely disrupted podocyte development in 40% of injected embryos. Co-overexpression of the two genes potently induced endogenous nphs2 expression in zebrafish podocytes. We found that the NPHS2 promoter also contains a cis-acting Lmx1b-FoxC motif that binds LMX1B and FoxC2. Furthermore, a genome-wide search identified several genes that carry the Lmx1b-FoxC motif in their promoter regions. Among these candidates, motif-driven podocyte enhancer activity of CCNC and MEIS2 was functionally analyzed in vivo. Our results show that podocyte expression of some genes is combinatorially regulated by two transcription factors interacting synergistically with a common enhancer. This finding provides insights into transcriptional mechanisms required for normal and pathologic podocyte functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.