FAK-Src signalling is important to renal collecting duct morphogenesis: discovery using a hierarchical screening technique

Summary This report describes a hierarchical screening technique for identification of pathways that control the morphogenesis of the renal collecting duct system. The multi-step screen involves a first round using a 2-dimensional, cell-line-based scrape-healing assay, then a second round using a 3-dimensional tubulogenesis assay; both of these rounds use new cell lines described in this report. The final stage is ex vivo organ culture. We demonstrate the utility of the screen by using it to identify the FAK–Src-pathway signalling as being important for collecting duct development, specifically for the cell proliferation on which this development depends

Tumour Suppressor Genes—One Hit Can Be Enough

A paper published in 1998 showed that loss of only one copy of the p53 tumor suppressor gene is sometimes enough to initiate carcinogenesi

LINking microRNAs, kidney development, and Wilms tumors

In this issue of Genes & Development, Urbach and colleagues (pp. 971–982) provide compelling data suggesting a role for LIN28 in the pathogenesis of a significant percentage of Wilms tumors. These data extend our insights in the genetics underlying Wilms tumor development and emphasize the importance of stemness and microRNA-mediated processes in the origins of these tumors

Nephrons require Rho-kinase for proximal-distal polarity development

Epithelial tubules must have the right length and pattern for proper function. In the nephron, planar cell polarity controls elongation along the proximal-distal axis. As the tubule lengthens, specialized segments (proximal, distal etc.) begin to differentiate along it. Other epithelia need Rho-kinase for planar cell polarity but it is not known whether Rho-kinase is involved in this way in the nephron. We show that Rho-kinase is essential for the morphogenesis of nephrons, specifically for correct cell orientation and volume. We use fluorescent reporter-models and progenitor-specific markers to demonstrate that inhibition of Rho-kinase prevents proper proximal-distal axis formation, causes segments to develop abnormally, and progenitor-cell segregation to fail. Our data demonstrate the importance of Rho-kinase in normal nephron tubulogenesis and patterning

The Yin and Yang of kidney development and Wilms’ tumours

Wilms’ tumor, or nephroblastoma, is the most common pediatric renal cancer. The tumors morphologically resemble embryonic kidneys with a disrupted architecture and are associated with undifferentiated metanephric precursors. Here, we discuss genetic and epigenetic findings in Wilms’ tumor in the context of renal development. Many of the genes implicated in Wilms’ tumorigenesis are involved in the control of nephron progenitors or the microRNA (miRNA) processing pathway. Whereas the first group of genes has been extensively studied in normal development, the second finding suggests important roles for miRNAs in general—and specific miRNAs in particular—in normal kidney development that still await further analysis. The recent identification of Wilms’ tumor cancer stem cells could provide a framework to integrate these pathways and translate them into new or improved therapeutic interventions