title: Mix.1/2-dependent control of FGF availability during gastrulation is essential for pronephros development in Xenopus.
abstract: Although FGFs are known to affect mesoderm patterning, their influence on intermediate mesoderm specification during gastrulation is ignored. Here, we show that pronephros precursors are exposed to FGF, but a strict control of FGF signals is necessary to allow pronephros development. We provide evidence that this control is mediated by the paired-like homeobox genes Mix.1 and Mix.2. Morpholino-based Mix.1/2 knockdown, or repression of Mix.1 target genes with an enRMix.1 construct, causes an expansion of FGF4 and FGF8 expression in the lateral marginal zone at gastrula stage, together with an inhibition of pronephros development at neurula and tailbud stages. Expression of the nephrogenic mesoderm markers Xlim-1 and XPax-8 can be rescued in Mix.1/2 morphants by intrablastocoelic injections of the FGFR inhibitor SU5402 at mid-gastrula stage, showing that inhibition of pronephros development results from an increase of FGF signalling. We further show that Mix.1 overexpression results in the down-regulation of FGF3, 4, 8 and XmyoD, in addition to Xbra. However, cells overexpressing Mix.1 can normally populate somites, indicating that Mix.1 does not affect their fate cell autonomously. These data support the idea that Mix.1/2 regulates levels and/or duration of FGF signals to which pronephros precursors are exposed during gastrulation.
authors.affiliation: UPMC Univ Paris 06, CNRS, Laboratoire de Biologie du Développement UMR 7622, 9 quai Saint-Bernard, 75005 Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Colas
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cartry
authors.forename: Isabelle
authors.initials: I
authors.lastname: Buisson
authors.forename: Muriel
authors.initials: M
authors.lastname: Umbhauer
authors.forename: James C
authors.initials: JC
authors.lastname: Smith
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Riou
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian; D005346:Fibroblast Growth Factors / Q000235:genetics*; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D007668:Kidney / Q000196:embryology* / Q000254:growth & development; D038081:Organogenesis; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D018398:Homeodomain Proteins; C531178:Mix.2 protein, Xenopus; C100368:Mix1 protein, Xenopus; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors