Retinoic acid signalling is required for specification of pronephric cell fate.
The mechanisms by which a subset of mesodermal cells are committed to a nephrogenic fate are largely unknown. In this study, we have investigated the role of retinoic acid (RA) signalling in this process using Xenopus laevis as a model system and Raldh2 knockout mice. Pronephros formation in Xenopus embryo is severely impaired when RA signalling is inhibited either through expression of a dominant-negative RA receptor, or by expressing the RA-catabolizing enzyme XCyp26 or through treatment with chemical inhibitors. Conversely, ectopic RA signalling expands the size of the pronephros. Using a transplantation assay that inhibits RA signalling specifically in pronephric precursors, we demonstrate that this signalling is required within this cell population. Timed antagonist treatments show that RA signalling is required during gastrulation for expression of Xlim-1 and XPax-8 in pronephric precursors. Moreover, experiments conducted with a protein synthesis inhibitor indicate that RA may directly regulate Xlim-1. Raldh2 knockout mouse embryos fail to initiate the expression of early kidney-specific genes, suggesting that implication of RA signalling in the early steps of kidney formation is evolutionary conserved in vertebrates.
Cartry
Jérôme
J
Laboratoire de Biologie du Développement, équipe Signalisation et Morphogenèse, UMR CNRS 7622, Université Paris VI, 9 quai Saint-Bernard, 75005 Paris, France.
Nichane
Massimo
M
Ribes
Vanessa
V
Colas
Alexandre
A
Riou
Jean-Francois
JF
Pieler
Tomas
T
Dollé
Pascal
P
Bellefroid
Eric J
EJ
Umbhauer
Muriel
M
D000445:Aldehyde Oxidoreductases / Q000172:deficiency; D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D005775:Gastrula / Q000166:cytology / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009399:Nephrons / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C543964:Lhx1 protein, Xenopus; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499500:Pax8 protein, Xenopus; C000607071:RARA protein, human; D012333:RNA, Messenger; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D029867:Xenopus Proteins; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse