Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development.
Mammalian nephrons form as a result of a complex morphogenesis and patterning of a simple epithelial precursor, the renal vesicle. Renal vesicles are established from a mesenchymal progenitor population in response to inductive signals. Several lines of evidence support the sequential roles of two Wnt family members, Wnt9b and Wnt4, in renal vesicle induction. Using genetic approaches to specifically manipulate the activity of beta-catenin within the mesenchymal progenitor pool in mice, we investigated the potential role of the canonical Wnt pathway in these inductive events. Progenitor-cell-specific removal of beta-catenin activity completely blocked both the formation of renal vesicles and the expected molecular signature of an earlier inductive response. By contrast, activation of stabilized beta-catenin in the same cell population causes ectopic expression of mesenchymal induction markers in vitro and functionally replaces the requirement for Wnt9b and Wnt4 in their inductive roles in vivo. Thus, canonical Wnt signaling is both necessary and sufficient for initiating and maintaining inductive pathways mediated by Wnt9b and Wnt4. However, the failure of induced mesenchyme with high levels of beta-catenin activity to form epithelial structures suggests that modulating canonical signaling may be crucial for the cellular transition to the renal vesicle.
Park
Joo-Seop
JS
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
Valerius
M Todd
MT
McMahon
Andrew P
AP
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D051153:Wnt Proteins; D051176:beta Catenin