Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4

Abstract

The kidney has been widely exploited as a model system for the study of tissue inductions regulating vertebrate organogenesis. Kidney development is initiated by the ingrowth of the Wolfian duct-derived ureteric bud into the presumptive kidney mesenchyme. In response to a signal from the ureter, mesenchymal cells condense, aggregate into pretubular clusters and undergo an epithelial conversion generating a simple tubule. This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron. We report here that the expression of Wnt-4, which encodes a secreted glycoprotein, correlates with, and is required for, kidney tubulogenesis. Mice lacking Wnt-4 activity fail to form pretubular cell aggregates; however, other aspects of mesenchymal and ureteric development are unaffected. Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development.

Molecular regulation of kidney development: is the answer blowing in the Wnt?

“…3a,e,i,m). Expression of Wnt4 is lost in wildtype tubules after the S-shaped body fuses to the collecting duct [45].…”

“…Analysis of mouse embryos by in situ hybridization has revealed the expression of six Wnts in the developing kidney: Wnt2b, Wnt4, Wnt6, Wnt7b, Wnt9b, and Wnt11 [9,[42][43][44][45]. Another eight Wnts have been shown to be present by sequencing of urogenital system cDNAs, with only Wnt5b identified as being specifically located in the kidney.…”

“…Wnt7b P1 images provided by Jing Yu. ag aggregate, wd Wolffian duct, ub ureteric bud, amp ureteric bud ampullae, cd collecting duct, cb commashaped bodies role in renal vesicle formation [45]. However, unlike Wnt9b, Wnt4 is required in the target cells, the so-called pre-tubular aggregates.…”

“…Wnt9b is necessary for MET but its mRNA continues to be expressed long after the last tubules have been induced [112]. Wnt4 is also necessary for mesenchymal-epithelial transition (MET), but its mRNA continues to be expressed in a polarized fashion within the comma-and S-shaped bodies [45]. Do either or both of these factors play additional roles in the growth, patterning or maintenance of the kidney epithelia?…”

Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

“…The recent ®nding that Frat can activate the Wnt signal transduction pathway through inhibition of GSK3 kinase activity, raises the possibility that the nephropathy in Em-pp-Frat1 transgenic mice is caused by ectopic Wnt signaling activity in the (developing) kidney (Yost et al, 1998). In this respect it is noteworthy that several Wnt family members 7b and 11) are expressed in the metanephric kidney, and that expression of Wnt-4 correlates with and is required for, kidney tubulogenesis (Stark et al, 1994;Kispert et al, 1996Kispert et al, , 1998.…”