Advances in Understanding the Genetic Mechanisms of Zebrafish Renal Multiciliated Cell Development

Wesselman, Hannah M.; Nguyen, Thanh Khoa; Chambers, Joseph M.; Drummond, B. J.; Wingert, Rebecca A.

doi:10.3390/jdb11010001

Cited by 9 publications

(6 citation statements)

References 140 publications

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“…Understanding ciliated cell types in specific tubular segments may provide insights into the relationship between cilia and kidney development [37,52]. Our study also demonstrates that ik mutants resulted in abnormal ciliary morphology in the pronephros, but interestingly, it was restricted only to proximal renal tubules and not distal tubules.…”

Section: Discussionmentioning

confidence: 54%

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1

Cho

Kwon

et al. 2023

Preprint

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Background The cilia are microtubule-based organelles that protrude from the cell surface. Abnormalities in cilia result in various ciliopathies, including polycystic kidney disease (PKD), Bardet-Biedl syndrome (BBS), and oral-facial-digital syndrome type I (OFD1), which show genetic defects associated with cilia formation. Although an increasing number of human diseases is attributed to ciliary defects, the functions or regulatory mechanisms of several ciliopathy genes remain unclear. Because cilia are deep in vivo, studying ciliogenesis is challenging. Here, we demonstrate that IK is essential for ciliogenesis in vivo. Results In the absence of IK, zebrafish embryos showed various ciliopathy phenotypes, such as body curvature, abnormal otoliths, and cyst formation in the kidney. RNA sequencing analysis showed that IK positively regulated ofd1 expression required for cilium assembly. Downregulation of ofd1 expression upon depletion of IK led to ciliary defects that was rescued by restoration of ofd1 expression. Interestingly, IK affected ciliogenesis particularly in the proximal tubule but not in the distal tubule in the kidney. Conclusions This study demonstrates the role of IK in ciliogenesis in vivo for the first time. Loss of IK in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Our findings on the IK–OFD1 axis provide new insights into the biological function of IK in clinical ciliopathy studies in humans.

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Section: Discussionmentioning

confidence: 54%

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1

Cho

Kwon

et al. 2023

Preprint

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“…Previous studies in the zebrafish pronephros have found that decreased MCC number can be associated with aberrations in ciliogenesis (e.g. decreased cilia outgrowth) ( Chambers et al, 2020b ; Marra et al, 2019a ; Wesselman et al, 2023a ).…”

Section: Resultsmentioning

confidence: 98%

Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis

et al. 2023

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Cilia are essential for the ontogeny and function of many tissues, including the kidney. Here, we report that transcription factor ERRγ ortholog estrogen related receptor gamma a (Esrrγa) is essential for renal cell fate choice and ciliogenesis in zebrafish. esrrγa deficiency altered proximodistal nephron patterning, decreased the multiciliated cell populace and disrupted ciliogenesis in the nephron, Kupffer's vesicle and otic vesicle. These phenotypes were consistent with interruptions in prostaglandin signaling, and we found that ciliogenesis was rescued by PGE2 or the cyclooxygenase enzyme Ptgs1. Genetic interaction revealed that peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (Ppargc1a), which acts upstream of Ptgs1-mediated prostaglandin synthesis, has a synergistic relationship with Esrrγa in the ciliogenic pathway. These ciliopathic phenotypes were also observed in mice lacking renal epithelial cell (REC) ERRγ, where significantly shorter cilia formed on proximal and distal tubule cells. Decreased cilia length preceded cyst formation in REC-ERRγ knockout mice, suggesting that ciliary changes occur early during pathogenesis. These data position Esrrγa as a novel link between ciliogenesis and nephrogenesis through regulation of prostaglandin signaling and cooperation with Ppargc1a.

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Section: Ra In Developmentmentioning

confidence: 99%

“…Within the nephron, a subpopulation of aptly named multiciliated cells (MCCs) project clusters of motile cilia into the tubule lumen and govern fluid flow [ 186 ]. MCCs are detectable via WISH as early as the 10-somite stage [ 186 ]. Much like the nephron tubule populations, MCCs are dependent on RA signaling for differentiation from the renal progenitors [ 178 ].…”

Section: Ra In Developmentmentioning

confidence: 99%

Zebrafish as a Model to Study Retinoic Acid Signaling in Development and Disease

Hawkins

Wingert

2023

Biomedicines

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Retinoic acid (RA) is a metabolite of vitamin A (retinol) that plays various roles in development to influence differentiation, patterning, and organogenesis. RA also serves as a crucial homeostatic regulator in adult tissues. The role of RA and its associated pathways are well conserved from zebrafish to humans in both development and disease. This makes the zebrafish a natural model for further interrogation into the functions of RA and RA-associated maladies for the sake of basic research, as well as human health. In this review, we explore both foundational and recent studies using zebrafish as a translational model for investigating RA from the molecular to the organismal scale.

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Advances in Understanding the Genetic Mechanisms of Zebrafish Renal Multiciliated Cell Development

Cited by 9 publications

References 140 publications

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1

Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis

Zebrafish as a Model to Study Retinoic Acid Signaling in Development and Disease

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