Renal organogenesis

We analyzed matrix metalloproteinase (MMP) production by 11-d embryonic mouse kidneys and the effects of these enzymes on subsequent renal organogenesis. In vivo, immunolocalization of metalloproteinases by laser scanning confocal microscopy and zymograms of kidney lysates showed that the mesenchyme of embryonic kidneys synthesized both MMP9 and MMP2 enzymes. In vitro, embryonic kidneys also secreted both enzymes when cultured in a medium devoid of hormone, growth factor, and serum for 24 h during which T-shaped branching of the ureter bud appeared. We then evaluated the role of MMP2 and MMP9 in kidney morphogenesis by adding anti-MMP2 or anti-MMP9 IgGs to the culture medium of 11-d kidneys for 24 or 72 h. Although it inhibited activity of the mouse enzyme, anti-MMP2 IgGs had no effect on kidney morphogenesis. In contrast, anti-MMP9 IgGs with enzyme-blocking activity impaired renal morphogenesis, in a concentration-dependent manner, by inhibiting T-shaped branching and further divisions of the ureter bud. This effect was irreversible, still observed after inductive events and reproduced by exogenous tissue inhibitor of metalloproteinase 1 (TIMP1), the natural inhibitor of MMP9. These data provide the first demonstration of MMP9 and MMP2 production in vivo by 11-d embryonic kidneys and further show that MMP9 is required in vitro for branching morphogenesis of the ureter bud.

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Transplantation of renal primordia: renal organogenesis

Pediatric Nephrology ◽

10.1007/s00467-007-0554-7 ◽

2007 ◽

Vol 22 (12) ◽

pp. 1991-1998 ◽

Cited By ~ 14

Author(s):

Marc R. Hammerman

Keyword(s):

Renal Organogenesis

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Macrophages restrict the nephrogenic field and promote endothelial connections during kidney development

eLife ◽

10.7554/elife.43271 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 13

Author(s):

David AD Munro ◽

Yishay Wineberg ◽

Julia Tarnick ◽

Chris S Vink ◽

Zhuan Li ◽

...

Keyword(s):

Progenitor Cell ◽

Kidney Development ◽

Developmental Abnormalities ◽

Macrophage Depletion ◽

Cell Clearance ◽

Galectin 3 ◽

Kidney Organogenesis ◽

Developing Kidney ◽

Nephron Progenitor ◽

Renal Organogenesis

The origins and functions of kidney macrophages in the adult have been explored, but their roles during development remain largely unknown. Here we characterise macrophage arrival, localisation, heterogeneity, and functions during kidney organogenesis. Using genetic approaches to ablate macrophages, we identify a role for macrophages in nephron progenitor cell clearance as mouse kidney development begins. Throughout renal organogenesis, most kidney macrophages are perivascular and express F4/80 and CD206. These macrophages are enriched for mRNAs linked to developmental processes, such as blood vessel morphogenesis. Using antibody-mediated macrophage-depletion, we show macrophages support vascular anastomoses in cultured kidney explants. We also characterise a subpopulation of galectin-3+ (Gal3+) myeloid cells within the developing kidney. Our findings may stimulate research into macrophage-based therapies for renal developmental abnormalities and have implications for the generation of bioengineered kidney tissues.

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Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice

AJP Renal Physiology ◽

10.1152/ajprenal.1995.268.1.f73 ◽

1995 ◽

Vol 268 (1) ◽

pp. F73-F81 ◽

Cited By ~ 12

Author(s):

C. M. Sorenson ◽

S. A. Rogers ◽

S. J. Korsmeyer ◽

M. R. Hammerman

Keyword(s):

Growth And Development ◽

Kidney Development ◽

Apoptotic Cell ◽

Mouse Embryos ◽

Kidney Morphology ◽

Metanephric Kidney ◽

Renal Size ◽

Culture Growth ◽

Renal Organogenesis

Apoptosis of the developing metanephric kidney plays an important role in renal organogenesis. The bcl-2 is an oncogene that inhibits apoptotic cell death in a variety of settings. The bcl-2 (-/-) mice complete embryonic development but, in contrast to bcl-2 (+/-) and bcl-2 (+/+) littermates, manifest growth retardation, hypopigmentation of hair, lymphoid apoptosis, abnormal kidney morphology, and renal failure postnatally. To provide insight into the mechanism for the latter abnormalities, we examined metanephric kidneys from bcl-2 (-/-), bcl-2 (+/-), and bcl-2 (+/+) mice, as well as embryonic day 12 (E12) mouse embryos, and compared growth and development of metanephroi in vitro. Kidneys from bcl-2 (+/-) mice developed normally. In contrast, development of kidneys from bcl-2 (-/-) mice was abnormal as reflected by a marked reduction of renal size in newborns compared with kidneys of bcl-2 (+/-) littermates. In addition, kidneys from bcl-2 (-/-) mice contained far fewer nephrons and had smaller nephrogenic zones. Although metanephroi obtained from E12 bcl-2 (+/-) and bcl-2 (-/-) mouse embryos were comparable in size, apoptosis of cells within metanephric blastemas of metanephroi from E12 bcl-2 (-/-) embryos was strikingly enhanced compared with that in blastemas of metanephroi from bcl-2 (+/-) embryos. During 3 days in culture, growth and development of metanephroi from bcl-2 (-/-) embryos were visibly reduced compared with those from bcl-2 (+/-) embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

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Demonstration of human kidney differentiation antigens with monoclonal antibodies.

Journal of Histochemistry & Cytochemistry ◽

10.1177/36.10.3047229 ◽

1988 ◽

Vol 36 (10) ◽

pp. 1255-1262 ◽

Cited By ~ 4

Author(s):

J J Candelier ◽

P Couillin ◽

G Bellon ◽

J Le Pendu ◽

P Eydoux ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Human Kidney ◽

Immunofluorescence Assay ◽

Basement Membranes ◽

Proximal Convoluted Tubule ◽

Differentiation Antigens ◽

Early Appearance ◽

Degree Of Differentiation ◽

Renal Organogenesis ◽

Labeling Pattern

Six human differentiation antigens (EE24.6, EG9.11, EG14.1, EI16.1, EK8.1, EK17.1) have been defined using monoclonal antibodies obtained from mice immunized with embryonic kidney cells. Their histologic distribution was determined on frozen sections of embryonic, fetal, and adult human kidneys by immunofluorescence assay. EE24.6, an ureteral bud marker, was detected only on the germ layer of mature kidney urothelium. EG9.11 and EG14.1 were detected on the S-shaped bodies and also on the adult proximal convoluted tubule for the former and the glomerular basement membrane for the latter. EI16.1, a marker of condensed mesenchyme, was detected only on epithelial cells of adult proximal convoluted tubule. EK8.1 was found in the mesangium, connective tissue, and with particularly dense labeling in the basement membranes. This labeling pattern was present throughout renal organogenesis. EK17.1 recognized both cell and plasma human fibronectins. Staining for all antibodies was nearly identical in mesonephros and metanephros. These results demonstate that some antigens follow their embryonic destiny. They indicate an antigenic similarity between the mesonephros and the metanephros and, therefore, a very early appearance of these antigens. During differentiation, these antigens concentrate on more defined structures, and staining became increased with an increased degree of differentiation.

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