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Publication : The GDNF target Vsnl1 marks the ureteric tip.

First Author  Ola R Year  2011
Journal  J Am Soc Nephrol Volume  22
Issue  2 Pages  274-84
PubMed ID  21289216 Mgi Jnum  J:191040
Mgi Id  MGI:5460841 Doi  10.1681/ASN.2010030316
Citation  Ola R, et al. (2011) The GDNF target Vsnl1 marks the ureteric tip. J Am Soc Nephrol 22(2):274-84
abstractText  Glial cell line-derived neurotrophic factor (GDNF) is indispensable for ureteric budding and branching. If applied exogenously, GDNF promotes ectopic ureteric buds from the Wolffian duct. Although several downstream effectors of GDNF are known, the identification of early response genes is incomplete. Here, microarray screening detected several GDNF-regulated genes in the Wolffian duct, including Visinin like 1 (Vsnl1), which encodes a neuronal calcium-sensor protein. We observed renal Vsnl1 expression exclusively in the ureteric epithelium, but not in Gdnf-null kidneys. In the tissue culture of Gdnf-deficient kidney primordium, exogenous GDNF and alternative bud inducers (FGF7 and follistatin) restored Vsnl1 expression. Hence, Vsnl1 characterizes the tip of the ureteric bud epithelium regardless of the inducer. In the tips, Vsnl1 showed a mosaic expression pattern that was mutually exclusive with beta-catenin transcriptional activation. Vsnl1 was downregulated in both beta-catenin-stabilized and beta-catenin-deficient kidneys. Moreover, in a mouse collecting duct cell line, Vsnl1 compromised beta-catenin stability, suggesting a counteracting relationship between Vsnl1 and beta-catenin. In summary, Vsnl1 marks ureteric bud tips in embryonic kidneys, and its mosaic pattern demonstrates a heterogeneity of cell types that may be critical for normal ureteric branching.
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