title: The GDNF target Vsnl1 marks the ureteric tip.
abstract: 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 β-catenin transcriptional activation. Vsnl1 was downregulated in both β-catenin-stabilized and β-catenin-deficient kidneys. Moreover, in a mouse collecting duct cell line, Vsnl1 compromised β-catenin stability, suggesting a counteracting relationship between Vsnl1 and β-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.
authors.affiliation: Biochemistry and Developmental Biology, Institute of Biomedicine, P.O. Box 63, Haartmaninkatu 8, University of Helsinki, FIN-00014, Finland.
authors.forename: Roxana
authors.initials: R
authors.lastname: Ola
authors.forename: Madis
authors.initials: M
authors.lastname: Jakobson
authors.forename: Jouni
authors.initials: J
authors.lastname: Kvist
authors.forename: Nina
authors.initials: N
authors.lastname: Perälä
authors.forename: Satu
authors.initials: S
authors.lastname: Kuure
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Braunewell
authors.forename: Darren
authors.initials: D
authors.lastname: Bridgewater
authors.forename: Norman D
authors.initials: ND
authors.lastname: Rosenblum
authors.forename: Dmitri
authors.initials: D
authors.lastname: Chilov
authors.forename: Tiina
authors.initials: T
authors.lastname: Immonen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Sainio
authors.forename: Hannu
authors.initials: H
authors.lastname: Sariola
mesh_terms: D000818:Animals; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051596:Neurocalcin / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D014513:Ureter / Q000196:embryology*; D051176:beta Catenin / Q000502:physiology
chemical_list: D015415:Biomarkers; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051596:Neurocalcin; C496689:Vsnl1 protein, mouse; D051176:beta Catenin; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium