Molecular integration of casanova in the Nodal signalling pathway controlling endoderm formation.
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.
Aoki
Tazu O
TO
U 368 INSERM, Ecole Normale Supérieure, 46, rue d'Ulm, F-75230 Paris Cedex 05, France.
David
Nicolas B
NB
Minchiotti
Gabriella
G
Saint-Etienne
Laure
L
Dickmeis
Thomas
T
Persico
Graziella M
GM
Strähle
Uwe
U
Mourrain
Philippe
P
Rosa
Frédéric M
FM
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004707:Endoderm / Q000502:physiology*; D050992:GATA5 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008845:Microinjections; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D055457:Nodal Protein; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D055747:SOX Transcription Factors; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins
D015415:Biomarkers; D004268:DNA-Binding Proteins; D050992:GATA5 Transcription Factor; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D055457:Nodal Protein; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; D055747:SOX Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C494754:gata5 protein, zebrafish; C438614:sox32 protein, zebrafish; C110484:tdgf1 protein, zebrafish