Cis-regulatory analysis of nodal and maternal control of dorsal-ventral axis formation by Univin, a TGF-beta related to Vg1.
The TGF-beta family member Nodal is essential for specification of the dorsal-ventral axis of the sea urchin embryo, but the molecular factors regulating its expression are not known. Analysis of the nodal promoter is an excellent entry point to identify these factors and to dissect the regulatory logic driving dorsal-ventral axis specification. Using phylogenetic footprinting, we delineated two regulatory regions located in the 5' region of the nodal promoter and in the intron that are required for correct spatial expression and for autoregulation. The 5' regulatory region contains essential binding sites for homeodomain, bZIP, Oct, Tcf/Lef, Sox and Smad transcription factors, and a binding site for an unidentified spatial repressor possibly related to Myb. Soon after its initiation, nodal expression critically requires autoregulation by Nodal and signaling by the maternal TGF-beta Univin. We show that Univin is related to Vg1, that both Nodal and Univin signal through Alk4/5/7, and that zygotic expression of univin, like that of nodal, is dependent on SoxB1 function and Tcf/beta-catenin signaling. This work shows that Tcf, SoxB1 and Univin play essential roles in the regulation of nodal expression in the sea urchin and suggests that some of the regulatory interactions controlling nodal expression predate the chordates. The data are consistent with a model of nodal regulation in which a maternal TGF-beta acts in synergy with maternal transcription factors and with spatial repressors to establish the dorsal-ventral axis of the sea urchin embryo.
Range
Ryan
R
UMR 7009 CNRS, Université Pierre et Marie Curie (Paris 6 Observatoire Océanologique, 06230 Villefranche-sur-mer, France.
Lapraz
François
F
Quirin
Magali
M
Marro
Sophie
S
Besnardeau
Lydia
L
Lepage
Thierry
T
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019521:Body Patterning; D004252:DNA Mutational Analysis; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D007438:Introns; D008969:Molecular Sequence Data; D055457:Nodal Protein; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid; D055748:SOXB1 Transcription Factors; D012617:Sea Urchins / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; D055457:Nodal Protein; D055748:SOXB1 Transcription Factors; D051785:Smad Proteins; C402390:SoxB1 protein, Strongylocentrotus purpuratus; D051820:TCF Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C090547:univin