title: Eya-six are necessary for survival of nephrogenic cord progenitors and inducing nephric duct development before ureteric bud formation.
abstract: BACKGROUND
  Specification of the metanephric mesenchyme is a central step of kidney development as this mesenchyme promotes nephric duct induction to form a ureteric bud near its caudal end. Before ureteric bud formation, the caudal nephric duct swells to form a pseudostratified epithelial domain that later emerges as the tip of the bud. However, the signals that promote the formation of the transient epithelial domain remain unclear. Here, we investigated the early roles of the mesenchymal factor Six family and its cofactor Eya on the initial induction of nephric duct development.
  
  
  RESULTS
  The nephrogenic progenitor population is initially present but significantly reduced in mice lacking both Six1 and Six4 and undertakes an abnormal cell death pathway to be completely eliminated by ∼E10.5-E11.0, similar to that observed in Eya1(-/-) embryos. Consequently, the nephric duct fails to be induced to undergo normal proliferation to pseudostratify and form the ureteric bud in Six1(-/-) ;Six4(-/-) or Eya1(-/-) embryos.
  
  
  CONCLUSIONS
  Our data support a model where Eya-Six may form a complex to regulate nephron progenitor cell development before metanephric specification and are critical mesenchymal factors for inducing nephric duct development.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jinshu
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.|Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Pin-Xian
authors.initials: PX
authors.lastname: Xu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009399:Nephrons / Q000166:cytology / Q000196:embryology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014513:Ureter / Q000166:cytology / Q000196:embryology*
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C490947:Six1 protein, mouse; C098490:Six4 protein, mouse; D015534:Trans-Activators; C501156:Eya1 protein, mouse; D017027:Protein Tyrosine Phosphatases
keywords: Eya1; Six1/4; metanephric mesenchyme; nephric duct; nephrogenic cord; pseudostratification; ureteric bud