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Microbead Implantation in the Zebrafish Embryo
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Fgfr2 is integral for bladder mesenchyme patterning and function.

K A Walker1, Y Ikeda2, I Zabbarova2

  • 1Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;

American Journal of Physiology. Renal Physiology
|February 7, 2015
PubMed
Summary
This summary is machine-generated.

Loss of fibroblast growth factor receptor 2 (Fgfr2) in bladder mesenchyme disrupts bladder development, causing abnormal morphology, reduced contractility, and decreased compliance in mice.

Keywords:
bladder developmentbladder dysfunctionfibroblast growth factor receptor 2

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Area of Science:

  • Urology
  • Developmental Biology
  • Genetics

Background:

  • Urothelial signals, like sonic hedgehog (Shh), influence bladder mesenchyme differentiation.
  • Fibroblast growth factor receptor 2 (Fgfr2) is crucial for kidney and ureter mesenchymal development.

Purpose of the Study:

  • To investigate the role of Fgfr2 specifically within the bladder mesenchyme during development.
  • To determine the impact of Fgfr2 deletion in bladder mesenchyme on bladder structure and function.

Main Methods:

  • Utilized Tbx18cre mice for conditional deletion of Fgfr2 in bladder mesenchyme (Fgfr2(BM-/-)).
  • Employed a multi-modal approach including 3D reconstruction, molecular analyses (qPCR, in situ hybridization, ELISA, immunoblot), and functional assays (ex vivo bladder sheets, in vivo cystometry).

Main Results:

  • Fgfr2(BM-/-) bladders showed thin muscle layers, thickened lamina propria with increased collagen, and evidence of cell fate switching.
  • Postnatal development revealed progressive muscle loss and increased collagen in Fgfr2(BM-/-) bladders.
  • Functional studies demonstrated decreased contractility, increased passive tension, and impaired bladder function (high pressures, short intervals) in mutants.

Conclusions:

  • Loss of Fgfr2 in bladder mesenchyme significantly impairs bladder development and function.
  • Fgfr2 deficiency leads to altered bladder wall composition and mechanical properties.
  • The findings highlight Fgfr2 as a critical regulator of bladder mesenchymal development and homeostasis.