What are the inductive functions of the notochord?
- important in the formation of many axial structures (Shh)
- induces overlying ectoderm to convert to neural ectoderm
- specifies identity of certain cells within the early nervous system
- transforms certain mesodermal cells of the somites into vertebral bodies
- stimulates earliest steps in the development of the pancreas
What transcription factors and signals does the notochord utilize to induce ectoderm to convert to neural ectoderm?
- transcription factors: Foxa-2 and Goosecoid
- signals: noggin and chordin
What is the prechordal plate?
- aka head organizer
- formed by early cells that pass through the primitive node
- source of signals such as Shh involved in the ventral patterning of the forebrain
- source of signals important for the survival of neural crest cells that emigrate from the early forebrain
What are the steps in the formation of the notochord?
- primitive node provides the source of cells that will form the notochord
- cellular precursors of the notochord migrate anteriorly and are then left behind as a rodlike aggregation as the primitive streak regresses
- notochordal cells fuse with flanking endodermal cells and temporarily form a neuroenteric canal
- notochordal cells separate from the endoderm and aggregate to form a solid definitive notochord
What does Wnt3 do?
-acts on epiblast cells and induces the expression of nodal
What do Lefty1 and Cer1 do?
-blocks nodal in anterior epiblast and confines its expression to the posterior epiblast
What does Nodal do?
- establishes a posterior signaling center which induces formation of the primitive streak (pre-streak)
- establish left-right symmetry (early primitive streak stage)
What doe Cerebrus-like do?
- early primitive streak stage
- inhibits development of posterior structures
What does DKK-1 do?
- blocks Wnt, early primitive streak stage
- inhibits development of posterior structures
What do Otx-2 and Lim-1 do?
- early primitive streak stage
- associated with induction of anterior CNS/head
What do Noggin and Chordin do?
- primitive node
- neural inducer
What does Goosecoid act on and what does it do?
- acts on chordin and noggin
- activates genes
What does Foxa-2 do?
- establishment of primitive node
- initiates notochord function
- establishes midline structures cranial to nodal
- in late primitive streak stage acts on chordin and noggin to activate genes
What does Brachyury do?
- notochord formation
- normal movement of cells through primitive streak
What does SHH do?
- induces axial structures (prechordial plate)
- neural inducer (notochord)
What does Cerebrus-related 1 do?
-normal head formation
What does retinoic acid, Wnt, and FGF do in the later primitive streak stage?
- targets Cdx
- induces Hox
What does the amphibian dorsal lip do?
-dorsal lip is organizer bc it organizes the formation of the embryo
What is the difference between determination and differentiation?
Determination: a process by which a cell or part of an embryo becomes restricted to a given developmental pathway. The point a cell becomes committed to a specific cell line.
Differentiation: a complex of changes involved in the progressive specialization of structure and function, often resulting in the formation of luxury molecules.
What are some examples of body asymmetry?
- heart
- looping of gut
- liver
- spleen
- lung lobation
What are the factors that determine left-right asymmetry?
-first sign of asymmetry involves the beating of cilia around the primitive node
+results in a directional current and expression of TGF-beta molecules (Nodal and Lefty-1)
-asymmetrical current occurs between 2 and 6 somite stage in mouse
How do nodal and lefty-1 for left-right asymmetry? What additional factors are used?
- nodal: symmetry breaking molecule in the left side of the embryo, swept to left side of primitive node by ciliary current, stimulates gene pathways through Pitx-2
- lefty-1: left side of the primitive streak, blocks diffusion of molecules to the right side
- Shh, retinoic acid, FGF-8
