Wnt5a Is Necessary for Normal Kidney Development in Zebrafish and Mice

An intact renin-angiotensin system involving ANG II type 1 (AT1) receptors is crucial for normal kidney development. It is still unclear in which cell types AT1 receptor signaling is required for normal kidney development, maturation, and function. Because all kidney cells deriving from stroma progenitor cells express AT1 receptors and because stromal cells fundamentally influence nephrogenesis and tubular maturation, we investigated the relevance of AT1 receptors in stromal progenitors and their descendants for renal development and function. For this aim, we generated and analyzed mice with conditional deletion of AT1A receptor in the FoxD1 cell lineage in combination with global disruption of the AT1B receptor gene. These FoxD1-AT1ko mice developed normally. Their kidneys showed neither structural nor functional abnormalities compared with wild-type mice, whereas in isolated perfused FoxD1-AT1ko kidneys, the vasoconstrictor and renin inhibitory effects of ANG II were absent. In vivo, however, plasma renin concentration and renal renin expression were normal in FoxD1-AT1ko mice, as were blood pressure and glomerular filtration rate. These findings suggest that a strong reduction of AT1 receptors in renal stromal progenitors and their descendants does not disturb normal kidney development.

Download Full-text

Expression of PKD1 and PKD2 Transcripts and Proteins in Human Embryo and during Normal Kidney Development

American Journal Of Pathology ◽

10.1016/s0002-9440(10)64919-x ◽

2002 ◽

Vol 160 (3) ◽

pp. 973-983 ◽

Cited By ~ 76

Author(s):

Véronique Chauvet ◽

Feng Qian ◽

Nicolas Boute ◽

Yiqiang Cai ◽

Bunyong Phakdeekitacharoen ◽

...

Keyword(s):

Human Embryo ◽

Kidney Development ◽

Normal Kidney

Download Full-text

Growth Hormone and IGF1 Actions in Kidney Development and Function

Cells ◽

10.3390/cells10123371 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3371

Author(s):

Evgenia Gurevich ◽

Yael Segev ◽

Daniel Landau

Keyword(s):

Growth Hormone ◽

Kidney Development ◽

Transgenic Animal ◽

Calcium Handling ◽

Normal Kidney ◽

Kidney Hypertrophy ◽

Transgenic Animal Models ◽

And Function ◽

Rhgh Treatment ◽

Gh Excess

Growth hormone (GH) exerts multiple effects on different organs including the kidneys, either directly or via its main mediator, insulin-like-growth factor-1 (IGF-1). The GH/IGF1 system plays a key role in normal kidney development, glomerular hemodynamic regulation, as well as tubular water, sodium, phosphate, and calcium handling. Transgenic animal models demonstrated that GH excess (and not IGF1) may lead to hyperfiltration, albuminuria, and glomerulosclerosis. GH and IGF-1 play a significant role in the early development of diabetic nephropathy, as well as in compensatory kidney hypertrophy after unilateral nephrectomy. Chronic kidney disease (CKD) and its complications in children are associated with alterations in the GH/IGF1 axis, including growth retardation, related to a GH-resistant state, attributed to impaired kidney postreceptor GH-signaling and chronic inflammation. This may explain the safety of prolonged rhGH-treatment of short stature in CKD.

Download Full-text

Dynamin binding protein is required for Xenopus laevis kidney development

10.1101/414458 ◽

2018 ◽

Cited By ~ 1

Author(s):

Bridget D. DeLay ◽

Tanya A. Baldwin ◽

Rachel K. Miller

Keyword(s):

Xenopus Laevis ◽

Antisense Oligonucleotides ◽

Kidney Development ◽

Binding Protein ◽

Human Kidney ◽

Normal Kidney ◽

Similar Reduction ◽

Developmental Defects ◽

Early Markers ◽

Developing Kidney

ABSTRACTThe adult human kidney contains over one million nephrons, with each nephron consisting of a tube containing segments that have specialized functions in nutrient and water absorption and waste excretion. The embryonic kidney of Xenopus laevis consists of a single functional nephron composed of regions that are analogous to those found in the human nephron, making it a simple model for the study of nephrogenesis. The exocyst complex, which traffics proteins to the cell membrane in vesicles via CDC42, is essential for normal kidney development. Here, we show that the CDC42-GEF, dynamin binding protein (Dnmbp/Tuba), is essential for nephrogenesis in Xenopus. dnmbp is expressed in Xenopus embryo kidneys during development, and knockdown of Dnmbp using two separate morpholino antisense oligonucleotides results in reduced expression of late pronephric markers, whereas the expression of early markers of nephrogenesis remains unchanged. A greater reduction in expression of markers of differentiated distal and connecting tubules was seen in comparison to proximal tubule markers, indicating that Dnmbp reduction may have a greater impact on distal and connecting tubule differentiation. dnmbp knockout using CRISPR results in a similar reduction of late markers of pronephric tubulogenesis. Overexpression of dnmbp in the kidney also resulted in disrupted pronephric tubules, suggesting that dnmbp levels in the developing kidney are tightly regulated, with either increased or decreased levels leading to developmental defects. Together, these data suggest that Dnmbp is required for nephrogenesis.

Download Full-text

Normal Kidney Development

Diagnostic Pathology: Kidney Diseases ◽

10.1016/b978-0-323-37707-2.50011-2 ◽

2016 ◽

pp. 36-45

Keyword(s):

Kidney Development ◽

Normal Kidney

Download Full-text

Hypoxia-inducible factor prolyl-4-hydroxylation in FOXD1 lineage cells is essential for normal kidney development

Kidney International ◽

10.1016/j.kint.2017.06.015 ◽

2017 ◽

Vol 92 (6) ◽

pp. 1370-1383 ◽

Cited By ~ 8

Author(s):

Hanako Kobayashi ◽

Jiao Liu ◽

Andres A. Urrutia ◽

Mikhail Burmakin ◽

Ken Ishii ◽

...

Keyword(s):

Kidney Development ◽

Hypoxia Inducible Factor ◽

Normal Kidney

Download Full-text

Stromal prorenin receptor is critical for normal kidney development

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00320.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. R640-R650 ◽

Cited By ~ 3

Author(s):

Ihor V. Yosypiv ◽

Maria Luisa S. Sequeira-Lopez ◽

Renfang Song ◽

Alexandre De Goes Martini

Keyword(s):

Kidney Development ◽

Marked Decrease ◽

Specific Marker ◽

Normal Kidney ◽

Arterial Tree ◽

Conditional Deletion ◽

Nephron Progenitors ◽

Prorenin Receptor ◽

Accessory Subunit ◽

Metanephric Kidney

Formation of the metanephric kidney requires coordinated interaction among the stroma, ureteric bud, and cap mesenchyme. The transcription factor Foxd1, a specific marker of renal stromal cells, is critical for normal kidney development. The prorenin receptor (PRR), a receptor for renin and prorenin, is also an accessory subunit of the vacuolar proton pump V-ATPase. Global loss of PRR is embryonically lethal in mice, indicating an essential role of the PRR in embryonic development. Here, we report that conditional deletion of the PRR in Foxd1+ stromal progenitors in mice ( cKO) results in neonatal mortality. The kidneys of surviving mice show reduced expression of stromal markers Foxd1 and Meis1 and a marked decrease in arterial and arteriolar development with the subsequent decreased number of glomeruli, expansion of Six2+ nephron progenitors, and delay in nephron differentiation. Intrarenal arteries and arterioles in cKO mice were fewer and thinner and showed a marked decrease in the expression of renin, suggesting a central role for the PRR in the development of renin-expressing cells, which in turn are essential for the proper formation of the renal arterial tree. We conclude that stromal PRR is crucial for the appropriate differentiation of the renal arterial tree, which in turn may restrict excessive expansion of nephron progenitors to promote a coordinated and proper morphogenesis of the nephrovascular structures of the mammalian kidney.

Download Full-text