The EGF-CFC protein one-eyed pinhead is essential for nodal signaling.
The zebrafish EGF-CFC gene one-eyed pinhead (oep) is required zygotically for the formation of the ventral neuroectoderm, endoderm, and prechordal plate. Here we report that embryos lacking both maternal and zygotic Oep activity are defective in germ layer formation, organizer development, and the positioning of the anterior-posterior axis. An identical phenotype is displayed by double mutants for the nodal-related genes squint and cyclops. Mutations in oep eliminate the response to Squint and Cyclops overexpression but are suppressed by expression of Activin and activated forms of the type I receptor ActRIB and Smad2. Expression of the murine EGF-CFC gene cripto rescues oep mutants. These results suggest a conserved role for EGF-CFC proteins as essential extracellular cofactors for Nodal signaling during vertebrate development.
Gritsman
K
K
Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York 10016, USA.
Zhang
J
J
Cheng
S
S
Heckscher
E
E
Talbot
W S
WS
Schier
A F
AF
D028341:Activins; D000818:Animals; D019521:Body Patterning / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology*; D005260:Female; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007265:Inhibins / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics; D008648:Mesoderm / Q000502:physiology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051899:Smad2 Protein; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins; D015053:Zygote / Q000502:physiology
D004268:DNA-Binding Proteins; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051899:Smad2 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C497786:smad2 protein, zebrafish; C110484:tdgf1 protein, zebrafish; C096788:tdgf1.3 protein, Xenopus; D028341:Activins; D007265:Inhibins; D004815:Epidermal Growth Factor