Stromal–epithelial crosstalk regulates kidney progenitor cell differentiation

• Published in: Nature cell biology Vol. 15; no. 9; pp. 1035 - 1044
• Main Authors: Das, Amrita, Tanigawa, Shunsuke, Karner, Courtney M., Xin, Mei, Lum, Lawrence, Chen, Chuo, Olson, Eric N., Perantoni, Alan O., Carroll, Thomas J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2013; Nature Publishing Group
• Subjects: 631/136/142; 631/532/1360; Biology; Cadherins - genetics; Cadherins - metabolism; Cancer Research; Cell Biology; Cell Communication; Cell Differentiation; Cellular control mechanisms; Developmental Biology; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Expression Regulation; Humans; Internal medicine; Kidney - cytology; Kidney - growth & development; Kidney - metabolism; Kidneys; Life Sciences; Morphogenesis; Organ Size; Physiological aspects; Properties; Signal Transduction; Stem Cells; Stem Cells - cytology; Stem Cells - metabolism; Stromal Cells - cytology; Stromal Cells - metabolism; Transcription factors; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Wnt Proteins - genetics; Wnt Proteins - metabolism; United States; United States > US; Texas
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb2828

Present models suggest that the fate of the kidney epithelial progenitors is solely regulated by signals from the adjacent ureteric bud. The bud provides signals that regulate the survival, renewal and differentiation of these cells. Recent data suggest that Wnt9b, a ureteric-bud-derived factor, is sufficient for both progenitor cell renewal and differentiation. How the same molecule induces two seemingly contradictory processes is unknown. Here, we show that signals from the stromal fibroblasts cooperate with Wnt9b to promote differentiation of the progenitors. The atypical cadherin Fat4 encodes at least part of this stromal signal. Our data support a model whereby proper kidney size and function is regulated by balancing opposing signals from the ureteric bud and stroma to promote renewal and differentiation of the nephron progenitors. Carroll and colleagues show that the atypical cadherin Fat4 derived from stromal fibroblasts cooperates with Wnt9b produced by the ureteric bud to modulate self-renewal and differentiation of kidney progenitors.