Nephric lineage specification by Pax2 and Pax8.
The mammalian kidney develops in three successive steps from the initial pronephros via the mesonephros to the adult metanephros. Although the nephric lineage is specified during pronephros induction, no single regulator, including the transcription factor Pax2 or Pax8, has yet been identified to control this initial phase of kidney development. In this paper, we demonstrate that mouse embryos lacking both Pax2 and Pax8 are unable to form the pronephros or any later nephric structures. In these double-mutant embryos, the intermediate mesoderm does not undergo the mesenchymal-epithelial transitions required for nephric duct formation, fails to initiate the kidney-specific expression of Lim1 and c-Ret, and is lost by apoptosis 1 d after failed pronephric induction. Conversely, retroviral misexpression of Pax2 was sufficient to induce ectopic nephric structures in the intermediate mesoderm and genital ridge of chick embryos. Together, these data identify Pax2 and Pax8 as critical regulators that specify the nephric lineage.
Bouchard
Maxime
M
Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria.
Souabni
Abdallah
A
Mandler
Markus
M
Neubüser
Annette
A
Busslinger
Meinrad
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology*; D060850:LIM-Homeodomain Proteins; D008297:Male; D008648:Mesoderm / Q000166:cytology; D008650:Mesonephros / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014566:Urogenital System / Q000196:embryology / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C497319:Pax2 protein, mouse; C499496:Pax8 protein, mouse; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse