Molecular integration of casanova in the Nodal signalling pathway controlling endoderm formation
Author:
Aoki Tazu O.12, David Nicolas B.12, Minchiotti Gabriella3, Saint-Etienne Laure1, Dickmeis Thomas4, Persico Graziella M.3, Strähle Uwe4, Mourrain Philippe1, Rosa Frédéric M.12
Affiliation:
1. U 368 INSERM, Ecole Normale Supérieure, 46, rue d’Ulm, F-75230 Paris Cedex 05, France 2. These two authors contributed equally to this work 3. International Institute of Genetics and Biophysics, CNR, Via G. Marconi, 12-80125 Naples, Italy 4. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, F-67404 Illkirch Cedex, CU de Strasbourg, France
Abstract
Endoderm originates from a large endomesodermal field requiring Nodal signalling. The mechanisms that ensure segregation of endoderm from mesoderm are not fully understood. We first show that the timing and dose of Nodal activation are crucial for endoderm formation and the endoderm versus mesoderm fate choice, because sustained Nodal signalling is required to ensure endoderm formation but transient signalling is sufficient for mesoderm formation. In zebrafish, downstream of Nodal signals, three genes encoding transcription factors (faust, bonnie and clyde and the recently identified gene casanova) are required for endoderm formation and differentiation. However their positions within the pathway are not completely established. In the present work, we show that casanova is the earliest specification marker for endodermal cells and that its expression requires bonnie and clyde. Furthermore, we have analysed the molecular activities of casanova on endoderm formation and found that it can induce endodermal markers and repress mesodermal markers during gastrulation, as well as change the fate of marginal blastomeres to endoderm. Overexpression of casanova also restores endoderm markers in the absence of Nodal signalling. In addition, casanova efficiently restores later endodermal differentiation in these mutants, but this process requires, in addition, a partial activation of Nodal signalling.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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