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Related Experiment Videos

Nephric lineage specification by Pax2 and Pax8.

Maxime Bouchard1, Abdallah Souabni, Markus Mandler

  • 1Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.

Genes & Development
|November 19, 2002
PubMed
Summary

Transcription factors Pax2 and Pax8 are essential for early kidney development. Mouse embryos lacking both genes fail to form the pronephros and subsequent kidney structures, highlighting their critical role in nephric lineage specification.

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Area of Science:

  • Developmental biology
  • Genetics
  • Molecular biology

Background:

  • Mammalian kidney development involves sequential stages: pronephros, mesonephros, and metanephros.
  • The initial phase of kidney development (pronephros induction) requires specific regulators.
  • Previously, no single transcription factor was identified as the primary controller of this early stage.

Purpose of the Study:

  • To identify the key regulators responsible for initiating mammalian kidney development.
  • To investigate the roles of transcription factors Pax2 and Pax8 in pronephros formation.
  • To elucidate the molecular mechanisms underlying nephric lineage specification.

Main Methods:

  • Generation and analysis of mouse embryos lacking both Pax2 and Pax8 (double-mutant).

Related Experiment Videos

  • Examination of intermediate mesoderm development, including mesenchymal-epithelial transitions and gene expression (Lim1, c-Ret).
  • Assessment of cell fate, including apoptosis, in mutant embryos.
  • Functional studies using retroviral misexpression of Pax2 in chick embryos to induce ectopic nephric structures.

    • Main Results:

    • Mouse embryos lacking both Pax2 and Pax8 completely failed to form the pronephros and all subsequent nephric structures.
    • In double-mutant embryos, the intermediate mesoderm did not undergo necessary mesenchymal-epithelial transitions for nephric duct formation.
    • Failure to initiate kidney-specific gene expression (Lim1, c-Ret) and subsequent apoptosis of the intermediate mesoderm were observed.
    • Ectopic nephric structures were successfully induced in chick embryos by misexpressing Pax2, demonstrating its inductive capacity.

    Conclusions:

    • Transcription factors Pax2 and Pax8 are critical and essential regulators for the initial specification of the nephric lineage.
    • These factors control key early developmental events, including mesenchymal-epithelial transitions and survival of the intermediate mesoderm.
    • Pax2 and Pax8 act upstream of Lim1 and c-Ret in the genetic cascade of kidney development.