Developmental Renal Glomerular Defects at the Origin of Glomerulocystic Disease

The architecture of renal glomeruli is acquired through intricate and still poorly understood developmental steps. In our study we identify a crucial glomerular morphogenetic event in nephrogenesis that drives the remodeling/separation of the prospective vascular pole (the future entrance of the glo...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2020-10, Vol.33 (4), p.108304-108304, Article 108304
Main Authors: Fiorentino, Arianna, Christophorou, Armelle, Massa, Filippo, Garbay, Serge, Chiral, Magali, Ramsing, Mette, Rasmussen, Maria, Gubler, Marie-Claire, Bessieres, Bettina, Heidet, Laurence, Fischer, Evelyne, Pontoglio, Marco
Format: Article
Language:English
Subjects:
Biochemistry
Biochemistry, Molecular Biology
Biotechnology
Developmental Biology
HNF1B
Life Sciences
Losartan
morphogenesis
Neurobiology
Neurons and Cognition
Renal glomerular cysts
Renal Glomerulogenesis
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Summary:The architecture of renal glomeruli is acquired through intricate and still poorly understood developmental steps. In our study we identify a crucial glomerular morphogenetic event in nephrogenesis that drives the remodeling/separation of the prospective vascular pole (the future entrance of the glomerular arterioles) and the urinary pole (the tubular outflow). We demonstrate that this remodeling is genetically programmed. In fact, in mouse and human, the absence of HNF1B impairs the remodeling/separation of the two poles, leading to trapping and constriction of the tubular outflow inside the glomerulus. This aberration gives rise to obstructive glomerular dilations upon the initiation of primary urine production. In this context, we show that pharmacological decrease of glomerular filtration significantly contains cystic expansion. From a developmental point of view, our study discloses a crucial event on glomerular patterning affecting the “inside-outside” fate of the epithelia in the renal glomerulus. [Display omitted] •Renal glomerulogenesis implies the separation of vascular and urinary poles (VP/UP)•Pole separation is due to a protuberance whose emergence is controlled by HNF1B•The lack of the protuberance leads to UP trapping/constriction inside the VP•UP constriction prevents primary urine outflow and gives rise to glomerular cysts Renal glomerulogenesis, a complex morphogenetic process, is still not fully understood. Fiorentino et al. discover a genetically programmed process whose developmental dysfunction leads to self-strangled glomeruli that generate cysts upon filtration. This process tackles the need to separate the urinary and vascular poles in early nephron precursors.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2020.108304