scholarly journals Tfap2a is a novel gatekeeper of nephron differentiation during kidney development

Development ◽  
2019 ◽  
Vol 146 (13) ◽  
pp. dev172387 ◽  
Author(s):  
Brooke E. Chambers ◽  
Gary F. Gerlach ◽  
Eleanor G. Clark ◽  
Karen H. Chen ◽  
Anna E. Levesque ◽  
...  
Keyword(s):  
Kidney Development ◽  
Nephron Differentiation

Sulphated proteoglycan is required for collecting duct growth and branching but not nephron formation during kidney development

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1507-1517 ◽  
Author(s):  
J. Davies ◽  
M. Lyon ◽  
J. Gallagher ◽  
D. Garrod
Keyword(s):  
Kidney Development ◽  
Collecting Duct ◽  
Sodium Chlorate ◽  
Ureteric Bud ◽  
Nephron Differentiation ◽  
Bud Growth ◽  
Nephron Development ◽  
Sulphated Glycosaminoglycans ◽  
Sulphated Proteoglycan ◽  
Hepatocyte Growth

Kidney epithelia have separate origins; collecting ducts develop by ureteric bud growth and arborisation, nephrons by induced mesenchyme-epithelium transition. Both express sulphated glycosaminoglycans (GAGs) which are strikingly upregulated during nephron differentiation. However, sodium chlorate, an inhibitor of GAG sulphation, and the GAG-degrading enzymes heparitinase plus chondroitinase, did not prevent nephron development. In contrast, ureteric bud growth and branching were reversibly inhibited by the above reagents, the inhibition correlating quantitatively with sulphated GAG deprivation caused by a range of chlorate concentrations. Growth and branching could be independently restored during GAG deprivation by hepatocyte growth factor and phorbol-12-myristate acetate (PMA) respectively. Together these signalling effectors stimulated both branch initiation and growth. Thus growth and morphogenesis of ureteric bud involve distinct signalling pathways both regulated by GAGs.

Combinatorial control of the bradykinin B2 receptor promoter by p53, CREB, KLF-4, and CBP: implications for terminal nephron differentiation

2005 ◽  
Vol 288 (5) ◽  
pp. F899-F909 ◽  
Author(s):  
Zubaida Saifudeen ◽  
Susana Dipp ◽  
Hao Fan ◽  
Samir S. El-Dahr
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Dna Binding ◽  
Spatial Organization ◽  
Kidney Development ◽  
Collecting Duct ◽  
Proximal Promoter ◽  
Bradykinin B2 Receptor ◽  
Nephron Differentiation ◽  
Terminal Nephron

Despite a wealth of knowledge regarding the early steps of epithelial differentiation, little is known about the mechanisms responsible for terminal nephron differentiation. The bradykinin B2 receptor (B2R) regulates renal function and integrity, and its expression is induced during terminal nephron differentiation. This study investigates the transcriptional regulation of the B2R during kidney development. The rat B2R 5′-flanking region has a highly conserved cis-acting enhancer in the proximal promoter consisting of contiguous binding sites for the transcription factors cAMP response element binding protein (CREB), p53, and Krüppel-like factor (KLF-4). The B2R enhancer drives reporter gene expression in inner medullary collecting duct-3 cells but is considerably weaker in other cell types. Site-directed mutagenesis and expression of dominant negative mutants demonstrated the requirement of CREB DNA binding and Ser-133 phosphorylation for optimal enhancer function. Moreover, helical phasing experiments showed that disruption of the spatial organization of the enhancer inhibits B2R promoter activity. Several lines of evidence indicate that cooperative interactions among the three transcription factors occur in vivo during terminal nephron differentiation: 1) CREB, p53, and KLF-4 are coexpressed in B2R-positive differentiating cells; 2) the maturational expression of B2R correlates with CREB/p53/KLF-4 DNA-binding activity; 3) assembly of CREB, p53, and KLF-4 on chromatin at the endogenous B2R promoter is developmentally regulated and is accompanied by CBP recruitment and histone hyperacetylation; and 4) CREB and p53 occupancy of the B2R enhancer is cooperative. These results demonstrate that combinatorial interactions among the transcription factors, CREB, p53, and KLF-4, and the coactivator CBP, may be critical for the regulation of B2R gene expression during terminal nephron differentiation.

scholarly journals Renal blood flow and oxygenation drive nephron progenitor differentiation

2014 ◽  
Vol 307 (3) ◽  
pp. F337-F345 ◽  
Author(s):  
Christopher Rymer ◽  
Jose Paredes ◽  
Kimmo Halt ◽  
Caitlin Schaefer ◽  
John Wiersch ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Kidney Development ◽  
De Novo ◽  
Nephron Progenitors ◽  
Renal Vessels ◽  
Nephron Differentiation ◽  
Nephron Progenitor ◽  
Nephrogenic Zone

During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation.

Kidney development – consequences of disruption

2004 ◽  
pp. 14-15
Author(s):  
E Marelyn Wintour ◽  
Karen Moritz ◽  
Miodrag Dodic
Keyword(s):  
Kidney Development

Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function

2020 ◽  
pp. 1-11
Author(s):  
Thu N. A. Doan ◽  
Jessica F. Briffa ◽  
Aaron L. Phillips ◽  
Shalem Y. Leemaqz ◽  
Rachel A. Burton ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Intrauterine Growth Restriction ◽  
Kidney Development ◽  
Dna Methyltransferases ◽  
Growth Restriction ◽  
Epigenetic Mechanisms ◽  
Specific Expression ◽  
Maternal Line ◽  
Intrauterine Growth ◽  
Increased Risk

Abstract Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

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