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Related Experiment Videos

Vitamin A controls epithelial/mesenchymal interactions through Ret expression.

E Batourina1, S Gim, N Bello

  • 1Department of Urology, Columbia University, New York, New York, USA.

Nature Genetics
|January 4, 2001
PubMed
Summary
This summary is machine-generated.

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Vitamin A signaling and RET receptor tyrosine kinase form a crucial loop regulating kidney development. Restoring RET expression in mice lacking specific vitamin A receptors rescues renal malformations, highlighting a novel signaling pathway.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Mutations in the receptor tyrosine kinase RET gene cause Hirschsprung disease, cancer, and renal malformations.
  • Kidney development relies on reciprocal signaling between ureteric bud epithelium and metanephric mesenchyme.
  • Vitamin A deficiency is linked to embryonic abnormalities, including kidney malformations, mediated by retinoic acid receptors (RARs).

Purpose of the Study:

  • To investigate the role of vitamin A signaling and RET in kidney development.
  • To elucidate the interaction between stromal mesenchyme, ureteric bud, and RET signaling.
  • To determine if RET signaling can rescue renal defects caused by vitamin A pathway disruption.

Main Methods:

  • Generated and analyzed mice deficient for Rara and Rarb2 genes (Rara(-/-)Rarb2(-/-)).

Related Experiment Videos

  • Utilized genetic rescue by forcing expression of Ret in Rara(-/-)Rarb2(-/-) mice.
  • Observed and compared renal development, ureteric bud growth, and stromal cell patterning in wild-type and mutant mice.

    • Main Results:

    • Deletion of Rara and Rarb2 in stromal mesenchyme led to altered stromal patterning and impaired ureteric bud growth with reduced Ret expression.
    • Forced expression of Ret in Rara(-/-)Rarb2(-/-) mice genetically rescued renal development, restoring ureteric bud growth and stromal cell patterning.
    • Identified a novel reciprocal signaling loop: vitamin A-dependent stromal signals control ureteric bud Ret expression, and Ret-dependent ureteric bud signals control stromal patterning.

    Conclusions:

    • A novel reciprocal signaling loop exists between ureteric bud epithelium and stromal mesenchyme, dependent on RET and vitamin A.
    • Vitamin A signaling in stromal cells is essential for regulating RET expression in the ureteric bud.
    • RET signaling in the ureteric bud is critical for proper stromal cell patterning during kidney development.