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Vertebrate Embryonic Patterning 3. Molecular Basis of Spemann’s Organizer. Inducing Centers in the Blastula. “Spemann”. (General). Fate Map of Organizer and Nieuwkoop’s Center. Molecular Nature of the Organizer. Transcription Factors Diffusible Molecules BMP inhibitors Wnt inhibitors. - PowerPoint PPT Presentation
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Vertebrate Embryonic Patterning 3
Molecular Basis of Spemann’s Organizer
Inducing Centers in the Blastula
“Spemann”
(General)
Fate Map of Organizer and Nieuwkoop’s Center
Molecular Nature of the Organizer
• Transcription Factors
• Diffusible Molecules– BMP inhibitors– Wnt inhibitors
Goosecoid
• named based on homology to Drosophila gooseberry and bicoid homeodomain
• expressed in the organizer – dorsal blastopore lip
• activates txn of other organizer-specific genes e.g. Xotx2, Xnot, Xlim1, chordin, noggin, Xnr 1, 2, 4
Targeted Injections of Xenopus Embryos
Goosecoid Induces Secondary Axes
Injection of gsc into ventral vegetal blastomere at 8-16 cell stage induces a secondary axis. Both axes begin with the concentration of pigment at a blastopore lip (arrows). The 2° axis forms anterior head structures (cement gland)
BMP Inhibitors
ORGANIZER MOLECULES
Noggin – expressed in deep mesoderm of organizer that ultimately forms notochord
Chordin – expressed in deep mesoderm & pharyngeal endoderm that ultimately underlies head
Cerberus – expressed in organizer & endoderm ultimately forming head
BMP-4 Expression Pattern
St. 10.5vegetal view
dorsal lip
St. 11vegetal view
dorsal view
Noggin Expression Pattern
notochordDV
Noggin Rescues UV Ventralized Embryos UV
injectednoggin mRNA
lo
hi
Noggin cloned through a functional screen by Richard Harland.
Protein functions by binding to BMP2 & 4 and prevents their binding to their receptors.
Chordin Expression Pattern
St. 10 St. 10.5 St. 13
dorsal blastopore lip
blastoporeaxial mesoderm
prechordal plate
Chordin FunctionChordin also binds & sequesters BMP4
BMP Gradient formed by Opposing Activities of Chordin & Xolloid
Cerberus Expression Pattern
Cerberus Duplicates Axes! Who’d a Thunk It?
Cerberus Function
• Cerberus binds to – Xwnt-8 (ventral mesoderm)– BMP-4 (ventral ectoderm)– Xnr-1 (dorsal mesoderm)
Cerberus
Cer Double Axes Enhanced by Blocking Wnt, BMP, and Xnr Pathways
Follistatin
– binds to TGF- family ligands– blocks their interaction with receptors
Wnt Inhibitors
• Frisbee – Soluble protein that mimics the
frizzled wnt binding domain.
• Dickkopf – functions by sequestering wnts
• Cerberus – binds to wnts
Frisbee Expression
Frzb Function
Frisbee Causes Anteriorization
Frz & Fz are Members of Same Protein Superfamily Family
CRD= cysteine rich domain: conserved set of cys residues that give protein distinct 2° structure