Identification and comparative expression analysis of a second <i>wt1</i> gene in zebrafish

Bollig, Frank; Mehringer, Rebecca; Perner, Birgit; Hartung, C.; Schäfer, Matthias; Schartl, Manfred; Volff, Jean‐Nicolas; Winkler, Christoph; Englert, Christoph

doi:10.1002/dvdy.20645

Cited by 88 publications

(96 citation statements)

References 38 publications

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“…Renin-expressing cells are also in contact with Wilms tumor 1b-expressing glomerular primordial cells (Fig. 1, F and G) (3,56), as also shown by Laing et al (43) and Hoshijima and Hirose (24) with podocin and ren ISHs.…”

Section: Larval Fish Renin Characterizationsupporting

confidence: 79%

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Rider

Mullins

Verdon

et al. 2015

American Journal of Physiology-Renal Physiology

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Rider SA, Mullins LJ, Verdon RF, MacRae CA, Mullins JJ. Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium. Am J Physiol Renal Physiol 309: F531-F539, 2015. First published July 22, 2015 doi:10.1152/ajprenal.00247.2015.-Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and the mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation but was modulated by inhibition of angiotensin-converting enzyme and altered salinity. Our data in larval fish are consistent with conservation of renin's physiological functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signaling and the endothelium are essential for developmental renin expression. After inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are among the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions. renin; zebrafish; notch; endothelium; angiogenesis RENIN is the rate-limiting enzyme of the renin-angiotensin system (RAS). Mammalian ANG II, the effector of the RAS, is principally involved in blood pressure homeostasis by regulation of vasomotor tone and Na ϩ retention. ANG II also regulates cell proliferation and angiogenesis (12,22). Pathological activation of the RAS is associated with cardiovascular diseases, including hypertension and heart failure, and is consequently a major target of therapeutic agents (11).Renin and its cognate cells are required for normal renal development (2), including angiogenesis of the renal vascular tree (59). In mice, ablation of the renin gene or renin-expressing cells leads to renal developmental abnormalities (55,71,79). The vasculature of mammalian embryonic kidneys have a transient but extensive coverage of mural renin-expressing cells (17,31,32,47,63); however, their function is unclear. Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic re...

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Section: Larval Fish Renin Characterizationsupporting

confidence: 79%

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Rider

Mullins

Verdon

et al. 2015

American Journal of Physiology-Renal Physiology

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“…9,25,26 These cells migrate to the midline and express podocyte genes such nephrin and podocin. 6 In hnf1ba/b-deficient embryos at 24 hpf, the expression domain of wt1a and wt1b was ectopically expanded into the region where the PCT segment normally Figure 4C, arrowhead).…”

Section: Ectopic Podocyte Formation Occurs In Hnf1ba/b-deficient Embryosmentioning

confidence: 99%

HNF1β Is Essential for Nephron Segmentation during Nephrogenesis

Naylor

Przepiorski

Ren

et al. 2013

Journal of the American Society of Nephrology

113

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Nephrons comprise a blood filter and an epithelial tubule that is subdivided into proximal and distal segments, but what directs this patterning during kidney organogenesis is not well understood. Using zebrafish, we found that the HNF1b paralogues hnf1ba and hnf1bb, which encode homeodomain transcription factors, are essential for normal segmentation of nephrons. Embryos deficient in hnf1ba and hnf1bb did not express proximal and distal segment markers, yet still developed an epithelial tubule. Initiating hnf1ba/b expression required Pax2a and Pax8, but hnf1ba/b-deficient embryos did not exhibit the expected downregulation of pax2a and pax8 at later stages of development, suggesting complex regulatory loops involving these molecules. Embryos deficient in hnf1ba/b also did not express the irx3b transcription factor, which is responsible for differentiation of the first distal tubule segment. Reciprocally, embryos deficient in irx3b exhibited downregulation of hnf1ba/b transcripts in the distal early segment, suggesting a segment-specific regulatory circuit. Deficiency of hnf1ba/b also led to ectopic expansion of podocytes into the proximal tubule domain. Epistasis experiments showed that the formation of podocytes required wt1a, which encodes the Wilms' tumor suppressor-1 transcription factor, and rbpj, which encodes a mediator of canonical Notch signaling, downstream or parallel to hnf1ba/b. Taken together, these results suggest that Hnf1b factors are essential for normal segmentation of nephrons during kidney organogenesis.

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“…RNA in situ hybridization was performed using standard techniques 44 with the following antisense probes: six2.1 (this paper), bmp4, 20 wt1a, 21,45 pax2.1, 46 and ␣-tropomyosin. 47 Embryos were mounted in modified GMM mounting media 48 (100 ml Canada Balsam, SigmaAldrich, St. Louis, MO; ϩ 10 ml methyl salicylate, Sigma-Aldrich, St. Louis, MO) and photographed on a Leica DMRA scope equipped with a ProgRes C14 camera.…”

Section: Rna In Situ Hybridization Studies In Zebrafish Embryosmentioning

confidence: 99%

SIX2 and BMP4 Mutations Associate With Anomalous Kidney Development

Weber

Taylor

Winyard

et al. 2008

Journal of the American Society of Nephrology

180

138

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Renal hypodysplasia (RHD) is characterized by reduced kidney size and/or maldevelopment of the renal tissue following abnormal organogenesis. Mutations in renal developmental genes have been identified in a subset of affected individuals. Here, we report the first mutations in BMP4 and SIX2 identified in patients with RHD. We detected 3 BMP4 mutations in 5 RHD patients, and 3 SIX2 mutations in 5 different RHD patients. Overexpression assays in zebrafish demonstrated that these mutations affect the function of Bmp4 and Six2 in vivo. Overexpression of zebrafish six2.1 and bmp4 resulted in dorsalization and ventralization, respectively, suggesting opposing roles in mesendoderm formation. When mutant constructs containing the identified human mutations were overexpressed instead, these effects were attenuated. Morpholino knockdown of bmp4 and six2.1 affected glomerulogenesis, suggesting specific roles for these genes in the formation of the pronephros. In summary, these studies implicate conserved roles for Six2 and Bmp4 in the development of the renal system. Defects in these proteins could affect kidney development at multiple stages, leading to the congenital anomalies observed in patients with RHD.

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Identification and comparative expression analysis of a second wt1 gene in zebrafish

Cited by 88 publications

References 38 publications

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

HNF1β Is Essential for Nephron Segmentation during Nephrogenesis

SIX2 and BMP4 Mutations Associate With Anomalous Kidney Development

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