1 Flashcards
Describe the euglena animal model for the nervous system
- flagella enables movement
- eyespot responds to light as it contains pigments transducing photons from light. triggers more movement.
- receptive and responsive
How did the primordial nervous system arise?
Stretch-receptive myocytes spanning the outer ectoderm/epidermis proliferated and gave rise to an identical daughter cell and a non-identical sensorimotor cell with a more complex shape
DEFINE: neurosecretory cells
cells that secrete peptide hormones that are 9-12 amino acids long e.g. insulin, glucagon and somatostatin
Somatostatin
hormone that regulates myocytes
Hydra Nervous System
- sensory neurons span the ectoderm
- motor neurons located beneath the ectoderm. they receive input from sensory neurons and output to effector cells and other motor neurons
- neurosecretory cells
- 2 layered nervous system - information flows backwards and forwards between sensory and motor cells
- interneurons between sensory neurons and myocytes/motor neurons
- interneurons between neurosecretory cells and myocytes/motor neurons
- diffuse nerve net
- radial symmetry
flatworm nervous system
- more clustering and organisation of neurons
- bilateral symmetry
- non-segmented worm
What is the purpose of gangliation?
Clustering the same neurons together produces a larger response
support for nervous system evolution theory using c.elegans
- trace progeny of P cell = single cell
- P cell forms AB cell and P cell
- neurons and hypodermis are derived from AB cell so they share lineage
so nerve cells derived through specialisation of epidermis cells
Neurogenic
region of cells that will become the nervous system
Neuroblasts
dividing progenitors whose descendants will be neurons
How does the nervous system develop in the Drosophila embryo?
- layer of ectoderm lies next to neurogenic region
- gastrulation - migration of neurogenic region downwards. neurogenic region joins there as development proceeds
- neuroblasts delaminate and migrate inwards
- neuroblasts coalesce and form the ventral nerve cord
What do neuroblasts divide into?
- 2nd neuroblast - maintained as multipotent cell
- ganglion mother cell - gives rise to neurons and glia
Where does the hypothalamus develop in the early nervous system?
ventral forebrain
How long does it take for the chick embryo to form?
21 days
When are the first signs of neural differentiation seen in human embryos?
2 weeks
How does the nervous system end up inside in vertebrates?
- neural plate is a sheet of neural precursors
- neural plate is bounded by ectoderm on either side
- neural plate rolls up into neural tube
- layers of ectoderm are brought together and fuse above the neural tube
results in layer of skin overlying neural tube and encasing it
How are BMPs made?
made as long prodomain proteins that are cleaved by BMP1 into their active components
What is the vertebrate homolog of Screw
BMP7
What is the vertebrate homolog of Dpp
BMP4
What is the vertebrate homolog of tolloid
BMP1
What is the vertebrate homolog of Sog?
Chordin
Spina bifida
neural tube defect - neural tube does not close properly
Chordin
Noggin
Follistatin
secreted BMP antagonists
At what stage in the chick embryo can you see the neural plate + neural tube forming?
Stage 4-8
Where is the prechordal mesoderm and notochord derived from?
axial mesoderm
DEFINE: involution
an epithelial sheet rolls inwards to form an underlying layer
DEFINE: intercalation
rows of cells move between one another, creating an array of cells that is longer but thinner
Spemann and Mangold organiser graft in Xenopus
graft an organiser from donor newt into ectopic location in host newt
twinned embryo formed with a secondary neural axis
host cells induced to a neural identity
How are cells committed to an ectodermal fate?
- all ectoderm cells express and respond to BMP
- BMP binds to TGFb, which results in the phosphorylation of SMADs
- phosphorylated SMADs translocate to the nucleus and act in a transcriptional complex to upregulate Msx1, GATA1 and Vent = cell autonomous TFs
- turns on LEF1 = commits cells to epidermal fate
How are ectoderm cells induced to neural plate cells?
- the organiser expresses goosecoid and siamois
- autonomously upregulate chordin, noggin, follistain = secreted BMP antagonists
- inhibit BMP pathway in ectoderm cells adjacent to mesoderm
- another set of phosphorylated SMADs translocate to the nucleus and upregulate Sox TFs
- Sox autonomously upregulates neurogenin
- neurogenin autonomously upregulates neuroD
DEFINE: neurulation
formation of a neural tube from the neural plate
Describe the cell shapes changes involved in neurulation
- neuroepithelium initially consists of simple columnar epithelial cells with tight junctions between them
- neuroepithelial cell has apical-basal polarity. apical domain of neuroepithelial cell has a band of contractile f-actin
- band of f-actin contracts and pulls tight - cells constricted at that edge
- cell changes shape from flat shape to u shape structure
How does low folic acid in pregnant mothers result in spina bifida?
folate signalling to folate receptors expressed on the apical edges of the neuroepithelium = one of the key events resulting in F-actin constriction
Where are sensory derivatives e.g. the retina derived from?
Forebrain-like tissue
When are the main parts of the nervous system established in humans?
3-5 weeks
What does the forebrain give rise to?
Telencephalon and diencephalon
Why is the early neural plate ‘anterior’ in character?
Anterior endoderm and prechordal mesoderm are the first cells to undergo convergent extension underneath midline of neural tube
They induce anterior TFs
Activation-transformation model: forming forebrain vs hindbrain + spinal cord
- prechordal mesoderm/anterior endoderm extend under midline of neural plate and induce anterior TFs in neural plate
- prechordal mesoderm is followed by notochord
- notochord lies under posterior neural plate and induces back end of neural plate to proliferate, express posterior TFs and repress anterior TFs
- neural plate gets longer as the notochord continues to grow from the organiser
- leads to forebrain, hindbrain and spinal cord set up
Wnt antagonists
Cerberus
Frzb
Dickkoft
What signals are expressed in the anterior organiser
BMP antagonists
Wnt antagonists
What signals are expressed in the posterior organiser
BMP antagonists
Wnt gradient
FGF gradient
RA gradient
Retinoic acid mechanism of action in establishing AP patterning in neural tube
- RA diffuses through membrane and binds to cytoplasmic RA receptor
- RA-receptor complex enters nucleus and binds directly to promoters of Hox genes to upregulate their transcription
- RA gradient induces different patterns of Hox genes
Role of Hox genes
Specifies AP segment identity and provides positional information
DEFINE: homeodomain
DNA binding protein domain of 60 amino acids
DEFINE: rhombomeres
series of outbulges in the hindbrain region of the neural tube
these express a particular pattern of Hox genes which dictates the identity of the rhombomere
What Hox genes are expressed in rhombomere 4 and what structures forms in this region?
Hoxa1 and Hoxb2
Forms abducens nerve
Why is it difficult to determine the function of Hox genes?
Functional redundancy
- each Hox gene went through 2 lots of duplication - results in 4 homologous genes coding for proteins with the same function
- provides back up if there is a mutation in one gene
- have to knock out all genes to determine function = expensive
How is the midbrain formed?
Interaction at the boundary of hindbrain and forebrain cells
what is RNAseq used for?
reveals presence and quantity of RNA in a cell
describe the process of RNAseq
- mRNA is isolated in a single cell
- cDNA is obtained from mRNA using reverse transcriptase
- software is used to determine the genes expressed in each cell population
what are fusion protein constructs used for?
- visualise protein distribution in live cells/animals
forward genetics
phenotype ——–> gene
reverse genetics
phenotype ———> gene
During forward genetics, how is the mutated gene identified?
positional cloning
how are conditional knock outs performed?
- flank dna sequence of gene of interest with loxP sites
- cross with a mouse expressing cre recombinase under a tissue specific promoter or under a promoter controlled in a temporal manner by induction with a drug
- cre recombinase carries out homologous recombination
