Aquatic models of human ciliary diseases

Corkins, Mark E.; Krneta‐Stankic, Vanja; Kloc, Małgorzata; Miller, Rachel K.

doi:10.1002/dvg.23410

Cited by 7 publications

(5 citation statements)

References 151 publications

(165 reference statements)

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“…Although the zebrafish is an established and conserved model to study renal diseases and ciliopathies, questions remain regarding the conservation of ERRγ function specifically ( Corkins et al, 2021 ; Molinari and Sayer, 2020 ; Morales and Wingert, 2017 ). Our current work supports previous research suggesting that ERRγ contributes to kidney function ( Zhao et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…Candidate transcription factors like tbx2b may be of interest, as it operates downstream of ppargc1a in establishing distal cell fate identity ( Chambers et al, 2018 ; Drummond et al, 2017 ), as well as mecom , tbx2a , emx1 , gldc and esr2b , which are also essential for distal segment fate ( Drummond et al, 2017 ; Li et al, 2014 ; Morales et al, 2018 ; Weaver et al, 2022 ; Wesselman et al, 2023c ). Although continued kidney research in animal models such as zebrafish affords the opportunity to dissect gene functions and model renal diseases like ciliopathies, parallel studies in mammalian models are also essential ( Corkins et al, 2021 ; McKee and Wingert, 2015 ; Molinari and Sayer, 2020 ; Morales and Wingert, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis

et al. 2023

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“…The basal body is an important structure of the cilium. The basal body is made up of a centriole, which is the locus where cilia growth happens (Reese., 1965;Preble et al, 1999;Corkins et al, 2021). After the centriole is generated, basal bodies migrate and fuse with the apical surface of multiciliated cells.…”

Section: Emx2 Regulates Basal Body Development In Renal Ciliamentioning

confidence: 99%

Emx2 is an essential regulator of ciliated cell development across embryonic tissues

Nguyen,

Rodriguez,

Wesselman

et al. 2024

Preprint

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Cilia are hair-like organelles with vital physiological roles, and ciliogenesis defects underlie a range of severe congenital malformations and human diseases. Here, we report that theempty spiracles homeobox gene 2 (emx2)transcription factor is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffer's vesicle (KV), which establishes left/right axial pattern.emx2deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), revealing thatemx2is essential to properly establish several renal lineages as well. Further,emx2deficiency disrupted ciliogenesis on renal monociliated cells and MCCs, and led to aberrant basal body positioning in kidney cells. Interestingly, we discovered thatemx2deficiency was associated with reduced expression of key factors which regulate prostaglandin biosynthesis: the transcriptional regulatorperoxisome proliferator-activated receptor gamma 1 alpha (ppargc1a)and its downstream targetprostaglandin-endoperoxide synthase 1 (ptgs1), which encodes a crucial enzyme for production of the prostanoid ligand prostaglandin E2 (PGE2). Importantly, both ciliogenesis and renal fate changes were rescued whenemx2deficient embryos were provided with PGE2 or transcripts encodingptgs1orppargc1a. Taken together, our findings reveal new essential roles ofemx2in cilia development across several tissues, and identifyemx2as a critical, novel regulator of prostaglandin biosynthesis during renal development and ciliogenesis.

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“…These include lists of candidate genes and proteins, whose roles in multiciliogenesis are yet to be explored. Cross-species comparisons are bound to be useful given the high degree of conservation that appears to exist across mechanisms of MCC fate choice, differentiation, and ciliary development as well [ 7 , 8 , 9 , 10 , 11 , 12 , 15 , 21 ].…”

Section: Swimming Ahead: Prospects and Challenges For Future Studies ...mentioning

confidence: 99%

“…In more recent years, however, research in eukaryotes ranging from protists to metazoans, the latter from the simplest invertebrates to the most complex vertebrates, has heralded a growing series of landmark advances in our understanding of MCC genesis [ 7 , 8 , 9 , 10 , 11 , 12 ]. For example, the embryonic amphibian epidermis has been a powerful tool to study MCC development and mucociliary biology [ 13 , 14 , 15 ]. Likewise, the planarian flatworm has been employed as a useful model to study epidermal MCC formation, where ciliary/MCC function can be readily monitored by observing each animal’s locomotion [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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

Wesselman

Nguyen

Chambers

et al. 2022

JDB

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Cilia are microtubule-based organelles that project from the cell surface. In humans and other vertebrates, possession of a single cilium structure enables an assortment of cellular processes ranging from mechanosensation to fluid propulsion and locomotion. Interestingly, cells can possess a single cilium or many more, where so-called multiciliated cells (MCCs) possess apical membrane complexes with several dozen or even hundreds of motile cilia that beat in a coordinated fashion. Development of MCCs is, therefore, integral to control fluid flow and/or cellular movement in various physiological processes. As such, MCC dysfunction is associated with numerous pathological states. Understanding MCC ontogeny can be used to address congenital birth defects as well as acquired disease conditions. Today, researchers used both in vitro and in vivo experimental models to address our knowledge gaps about MCC specification and differentiation. In this review, we summarize recent discoveries from our lab and others that have illuminated new insights regarding the genetic pathways that direct MCC ontogeny in the embryonic kidney using the power of the zebrafish animal model.

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Aquatic models of human ciliary diseases

Cited by 7 publications

References 151 publications

Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis

Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis

Emx2 is an essential regulator of ciliated cell development across embryonic tissues

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

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