Week 4 Flashcards
Patterning along the AP axis. There are cards about the forebrain, midbrain and hindbrain developing in the telencephalon etc.
Which of the brain areas does:
a) Forebrain
b) Midbrain
c) Hindbrain
- develop into.
Going further, what do the 5 vesicles then go on to constitute specifically?
a) Forebrain:
- Telencephalon
- Dienchephalon
b) Midbrain:
- Goes straight to the Tectum and Substantis nigra
c) Hindbrain:
- Mesencephalon
- Myelcephalon
Telencephalon -> Cerebrum, hippocampus
Diencephalon -> Thalamus, hypothalamus, retina
Midbrian -> Substantis nigra
Mesencephalon -> Pons and Cerebellum
Myelcephalon -> Medulla
What are the two morphogens that influence AP axis development in drosophila
Bicoid
Hunchback
What is the relationship/difference between Gap genes, Pair-rule genes and Hox genes?
NOTE: These are present in the DROSOPHILA
Gap genes:
- Among the earliest genes expressed after fertilisation
- T.Fs that control the initial broad patterning of the embryo along the AP axis by dividing it into large segments
- Gap genes include hunchback and bicoid
Pair-Rule Genes:
- Activated in response to the pattern established by gap genes
- Further refine segmentation
- Expression occurs in ALTERNATING segments along the AP axis to ensure delineated segments
- Examples: ftz and eve
Hox genes:
- Specify the identity of segments along the AP axis
- Activated by gap and pair-rule genes
- Determine unique characteristics of each segment and guide development of structures
- Spatial arrangement corresponds to their position on the chromosome (co-linearity)
Hox gene mutants have dramatic phenotypes. What are they?
Segment duplication
What is a common feature of gap gene mutants?
Segment deletion
Hox genes are conserved in vertebrates.
How are they regulated?
Through early graded signals involving morphogens:
- Wnt
- RA
- FGF
- TGF-beta
These graded signals that influence Hox genes come from the mesoderm DURING neural induction
Match the function to the group of signalling molecules:
a) Induction of neural plate formation
b) Further graded posteriorising signals
c) Extreme anterior (forebrain) signal (needed to protect the anterior from the posteriorising signals)
- Cerberus
- BMP inhibitors
- Wnt, Retinoic Acid (RA), FGF
a) BMP inhibitors
b) Wnt, RA, FGF
c) Cerberus
What is the retinoic acid signal pathway? (easy)
- Fat soluble
- Diffuses through membrane + acts on cytosol receptor
What is an exception to the Hox gene system? E.g., where is not patterned by this system?
The anterior brain!
- A separate set of antagonistic T.Fs produce unique, overlapping domains that give regional identity
In drosophila, how to neuroblasts gain their identity?
Their position on the AP AND DV axes gives them their identity
In drosophila, each segment is divided into 2 subsegments, A and P cells. P cells express ‘engrailed’.
Interactions between A and P cells lead to 2 new signals being produced.
What are they and what do they do?
- WG: Wingless
- HH: Hedgehog
These signals diffuse to create local concentration gradients IN the segments
In the drosophila neural tube, the DV axis is set up by the production of 2 antagonistic signal proteins.
What are they, and what is the confusing T.F that influences them?
(whatare the homologues in vertebrates?)
- DPP (the homologue of BMP)
- SOG (homologue of chordin)
DORSAL is the T.F for ventral patterning
What are columnar genes?
And what are some of the T.Fs they encode?
- Columnar genes form AP columns that encode homeodomain T.Fs
Some examples are:
-msh
- ind
- vnd
Based on the information above, explain how the integration of patterning information in 2 dimensions leads to neuroblasts getting their unique identity from their location
- Columnar genes give neuroblasts their DV location
- Segmentation genes give them their AP location
What is the ‘Isthmic organiser’ in terms of vertebrate anterior neural tube formation?
- It forms at the boundary of the midbrain and hindbrain.
- It is the name of this area, it becomes a new signalling centre for LOCAL patterning
- Secretes FGF8
- FGF8 patterns identity of neural genesis
Which signalling areas aid the formation of the DV axis / neural tube in vertebrates?
- Signalling from the mesoderm is important for neural induction
- The notochord (underneath the neural tube) is important for patterning of the neural tube and midline localisation
Outline the role of Shh in vertebrates in terms of basic transduction mechanism
How are Shh (vertebrates) and HH (drosophila) differentin terms of where they are transduced?
- Binds patched receptor
- Removes patched inhibition of smoothened
- smoothened then activates GLI (T.F.)
- Shh is transduced in the cells cilium in vertebrates where as HH is in the cytosol
How are the roof plate and floor plate of the neural tube induced?
And what happens once they have been induced in terms of signalling?
Roof plate:
- Lateral BMP signal in vertebrates (DPP in drosophila)
Floor plate:
- Shh signal from the notochord
Once they have been induced, the roof plate becomes the SOURCE of BMP and the floor plate becomes the SOURCE of SHH WITHIN the neural tube
SHH from the floor plate is a morphogen for a)_________ neural fates, BMP from the roof plate is a morphogen for b)________ neural fates
a) Ventral
b) Dorsal
SHH regulates expression domains of T.Fs, meaning that different concentrations of SHH either activate or repress a certain gene.
Genes in Class I: In order of repressed from Lowest conc of SHH required at the top to most
- Pax7
- Dbx1
- Dbx2
- Irx3
- Pax6
Class II Genes:
- Nkx6.1
- Nkx2.2 (vnd in drosophila)
What is the difference between class I and class II?
And what is the outcome of these expression domains?
- Class I are normally ON but are repressed by different concentrations of SHH
- Class II are normally OFF but are activated by different concentrations of SHH
The outcome is that the combination of genes expressed in each domain is a homeodomain code for the progenitor domain
Use motor neurons to give an example of how AP and DV signals are integrated in the vertebrate nervous system
- Motor neurons are formed ventrally along the whole neural tube (Nkx genes)
- They also have different identities along the AP axis (Hox genes)
In drosophila, ectodermal cells act as the neural progenitors.
What are the qualities of neural progenitors in general?
What 2 cell types can they turn into if they commit to a neural fate?
Proliferative and multipotent
Sense organ precursor
Neuroblast
Refresh: What are the specific
a) segmentation genes
b) columnar genes
That give AP and DV location (respectively) to drosophila neuroblasts?
a) gsb genes
b) vnd genes
Patterning genes regulate neurogenesis through the activation of pro-neural genes.
What are pro-neural genes?
Genes that plays a crucial role in the development of the nervous system, specifically the formation of neural progenitor cells and the subsequent differentiation of these cells into neurons
Regulation of pro-neural genes is what regulates neurogenesis
