3.3 Frog Development Flashcards
What does the Xenopus Organizer do?
- Ability to initiate the cell movements during grastrulation.
- Ability to self-differentiate into dorsal mesoderm.
- Ability to dorsalize surrounding mesoderm into paraxial mesoderm (Somites)
- Ability to dorsalize ectoderm and induce the formation of neural tube.
Exposure of cells to organizer
transplants in early garsula or late gastrula: trasplat an area of ectoderm into a new newt in the area that woukd form the epidermis
- EG: instead of neural ectoderm forms epidermis
- LG: presumptive neural cells forms neural plate (thereby causing 2 neural plates to form)
This shows that in early gastrula cells have not turned on permanently and don’t have a set fate (conditional).
In late gastrula they have already made up their mind (autonomous)
TGF-β Signaling (BMP mediated Smad activation)
- TGF-β binds to Receptor type II which allows the receptor type I to bind.
- The receptor complex then phosphorylate each other in trans-dependent manner and receptor is activated.
- The activated receptor phosphorylates Smad proteins.
- Smad1 and 5 are activated by BMP family of TGF-β
- Smad2 and 3 are activated by Activin or Nodal and TGF-β ligands
- The phosphorylated Smad proteins then bind to Smad4 and forms a transcription factor complex that enters the nucleus.
Mesoderm specification in frogs: “Four signal”
model
- A ventral vegetal signal (1) induces the cells above to become mesoderm.
- At the Nieuwkoop centre, a dorsalizing determinant (2) modifies this signal.
- A ventral mesodermal signal (3) ventralizes the mesoderm.
- The above signal (3) is inhibited (4) by dorsal signal from the Spemann organizer region
Specification of Mesoderm
- VegT mRNA activates VegT which activates Nodal.
- Nodal activates Eomesodermin
- VG1 mRNA activates Vg1 which activates Wnt inhibitors
- Eomesodermin and activated Smad2 (from the nodal) activates Veg T (feedforward loop)
- VegT has gone from maternal to mRNAs in presumptive endoderm to presumptive mesoderm
Vegetal cells serve two main functions
- Differentiation into Endoderm
- Induce the cells immediately above them to become the mesoderm
- The mechanism of this induction is the presence of maternal VegT mRNA that becomes aproportioned to the vegetal cells during the cortical rotation.
- VegT is a transcription factor that is critical for both the functions that vegetal cells serve.
Mesoderm Induction by Vegetal
Cells
- Late blastula, VegT and Veg1 in vegetal hem and B-cat in dorsal region
- B-cat acts with VegT/Veg1 to activate Xnr (xenopus nodal-related) genes.
- makes gradient of Xnr across endoderm, highest in dorsal region
- Eomes also lead to increase Xnr due to increase VegT
- mesoderm specified by gradient
- little/no Xnr = high BMP4 & Xwnt8 –>ventral mesoderm
- intermediate [ ] = lateral mesoderm
- high [ ] = organizer
- Xnr turns on Smad so Smad gradient
Smad gradient
- low [ ] = lateral/ventral mesoderm
- intermediate [ ] = goosecoid gene (orechordal mesoderm and notochord)
- high [ ] = Hhex gene (Foregut endoderm and Induce anterior brain Development)
Organizer contributes to 4-cell types
- Pharyngeal Endoderm
- Head Mesoderm (Prechordal Plate: Forebrain and Midbrain)
- Chordamesoderm (Notochord, hindbrain, trunk)
- Dorsal Blastopore lip remaining at the end of gastrulation become chordneural hinge that induces the :p of the tail.
EXPERIMENT:
- took tip of archenteron onto E.Gastula
- took cells from on top of archenteron
- transplanting to dif embryo
- took tip of archenteron onto E.Gastula
- took cells from on top of archenteron
- transplanting to dif embryo
- depending on where it was taken, it forms dif structures
- shows how regional specifificity is induced by organisum
- other part
- if young you get head, if old you get tail
- organiser is dynamic, it doesnt product same structures foreer
Diffusible protein antagonist of the organizer
Category 1: the bone morphogenetic protein (BMP) inhibitors (antagonists):
– Noggin
– Chordin and Nodal-related proteins
– Follista:n and ADMP (an:-dorsalizing morphogene:c protein)
Category 2: the Wnt (wingless type) protein inhibitors (antagonists)
– Cerberus
– Frzb (“frizbee”) and Dickkopf
Model for action of organizer
BMP4 is a ventralizing agent. Organizer secretes BMP4 antagonist. BMP4 elicits the gene expression in a concentration-dependent manner. In the region near organizer antagonist prevent BMP4 form binding and these cells become the notochord.
Wnt and BMP: Paracrine factor anatgonist to dis:ngush Head from the Tail
WNT & BMP = epidermis
[BMP] WNT = trunk and spinal cord
[BMP] [Wnt] = head and briain
Wnt blocked by chordin, noggin, etc.
BMP blocked by dikkopf, cerebrersus, etc
Induction of Ectoderm
- Wnt gradient specifies the anterior-posterior polarity.
* BMP gradient specifies the dorsal-ventral polarity.
