The ureters are a pair of straight tubes that mediate by peristaltic contractions the efficient removal of urine from the renal pelvis to the bladder. Functional insufficiency of their tissue compartments and physical obstruction along the path to the bladder lead to urinary back-flow, dilatation of the ureter (hydroureter) and of the renal pelvis (hydronephrosis). Congenital forms of these defects are frequently observed in human newborns defining an important task to understand normal and abnormal ureter development.
Our current work aims to unravel the molecular networks that orchestrate the development, homeostasis and regeneration of the mesenchymal and epithelial tissue compartments of the mouse ureter. We wish to explore how different signaling pathways (such as Notch, Wnt, Fgf, Bmp and Shh) interact with transcriptional regulators (including T-box transcription factors) to achieve the precise patterning and differentiation of fibroblasts and smooth muscle cells in the outer mesenchymal coat, and of basal, intermediate and superficial cells in the highly specialized inner epithelial lining, the urothelium. We use a combination of genetic and pharmacological manipulations to explore the molecular, cellular and physiological consequences of loss- and gain-of-gene functions.
All in all, this work may aid in establishing a paradigm for the molecular complexity guiding the development of a simple tubular organ. It may provide decisive insights into the etiology and possible molecular causes of congenital anomalies of the urinary tract, and allow the design of strategies for organ repair by tissue augmentation in vivo and tissue engineering in vitro.
Current ureter projects:
Molecular function of Tbx18 in ureter development
Functional analysis of Wnt signaling in the development of the ureteric mesenchyme
Molecular control of smooth muscle cell differentiation in the developing murine ureter
Molecular function of the T-box transcription factors TBX2 and TBX3 in the development and maintenance of the epithelial lining of the urinary tract in the mouse
Molecular control of early urothelial differentiation in the murine ureter
Function of the T-box transcription factors Tbx2 and Tbx3 in the development of the murine inner ear
Previous Funding: DFG
Regulation and molecular function of the T-box transcription factors Tbx2 and Tbx3 in the development of the murine lung
Previous funding: DFG