Abstract
BackgroundWnt11 is a member of the Wnt family of secreted signals controlling the early steps in ureteric bud (UB) branching. Due to the reported lethality of Wnt11 knockout embryos in utero, its role in later mammalian kidney organogenesis remains open. The presence of Wnt11 in the emerging tubular system suggests that it may have certain roles later in the development of the epithelial ductal system.ResultsThe Wnt11 knockout allele was backcrossed with the C57Bl6 strain for several generations to address possible differences in penetrance of the kidney phenotypes. Strikingly, around one third of the null mice with this inbred background survived to the postnatal stages. Many of them also reached adulthood, but urine and plasma analyses pointed out to compromised kidney function. Consistent with these data the tubules of the C57Bl6 Wnt11−/− mice appeared to be enlarged, and the optical projection tomography indicated changes in tubular convolution. Moreover, the C57Bl6 Wnt11−/− mice developed secondary glomerular cysts not observed in the controls. The failure of Wnt11 signaling reduced the expression of several genes implicated in kidney development, such as Wnt9b, Six2, Foxd1 and Hox10. Also Dvl2, an important PCP pathway component, was downregulated by more than 90 % due to Wnt11 deficiency in both the E16.5 and NB kidneys. Since all these genes take part in the control of UB, nephron and stromal progenitor cell differentiation, their disrupted expression may contribute to the observed anomalies in the kidney tubular system caused by Wnt11 deficiency.ConclusionsThe Wnt11 signal has roles at the later stages of kidney development, namely in coordinating the development of the tubular system. The C57Bl6 Wnt11−/− mouse generated here provides a model for studying the mechanisms behind tubular anomalies and glomerular cyst formation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-016-0131-z) contains supplementary material, which is available to authorized users.
Highlights
Wnt11 is a member of the Wnt family of secreted signals controlling the early steps in ureteric bud (UB) branching
Wnt11 is expressed in the epithelial tubular cells of the nephron and collecting duct during organogenesis During the early stages of kidney development the Wnt11 gene is expressed in the UB tip cells [2]
The investigations revealed that Wnt11 is expressed later, in the collecting duct (CD), the proximal tubule (PT), the terminal papillary duct cells, and the cells of the Bellini duct of the NB mice kidneys (Fig. 1a–d, arrows)
Summary
Wnt is a member of the Wnt family of secreted signals controlling the early steps in ureteric bud (UB) branching. The glomerulocystic kidney (GCK) disease is one of human renal cystic disorders which could be both sporadic and inherited [6], and has a higher occurrence in infants than in adults [7] Manifestation of this disease depends on the timing of exposure to the poorly characterized predisposing or causal factors influencing kidney development and function. GCK disease may be caused by defects within the glomeruli, it is more typical for the cysts to develop as a secondary consequence to the anomalies in the tubules Such anomalies can be connected with components of the Wnt signaling pathway, and with HNF1β transcription factor, which is involved in polycystic kidney disease (PKD), and the polycystic complex proteins [3, 4, 9,10,11]
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