Whole Module Flashcards
What is the reuslt ofo downreg of achaete and scute
Downregulation in delta expression
Define ganglination//how does It help
Coming together of many neurones into a cluster // allows communication between many neurones
Describe the type of nervous system seen in Hydra
Hydra are radially symmetrical and thus posees a nerve net rather than a central NS but without a brain or any type of cephalisation - this does however allow Hydra to respond to physical contact as well as detect food and other chemicals
Give examples of transcription factors that lead to BMP antgaonist expression
Gooesecoid, Xnot, Xlim
Four forces of axon guidance
Contact attraction, chemoattraction, contact repulsion, chemorepulsion
T or F newly born neurones are always dependent on NTs in order to suvive
F - not always - some havent yet extended axons
What is the name of the chemorepellant secreted by the roof plate directing axon gorwth away from it
BMP7
What is the model for how the NP gets longer
Activation transformation
Give examples of raly patterning molecules that are later used to direct axon growth
BMP7 initially involved in dorsalisation of the nueral tube and later directs comissural sensory relay neurones away from the roof plate /// Shhh used to specify the fates of ventral neurones and also used to guide axons to the floor plate
What assumptions does measuring the postsynaptic potential as a result of quantal increase of afferent stimulation require
The smallest size of resposnse seen in the target muscle corresponds to the innervation by a single afferent. Linear between stimulus size and postsynaptic response
What is the other name for permissive substrate
Contact attractant
Three factors that neural crest cell fate depends on
Position or origin of neural crest cells, time of generation and migratory pathway
What types of cell movement occur for the axial mesoderm to move under the neural plate
Involution, intercalation then they undergo convergent extension
Can growth cones adhere to non permissive substrates
No
In a sponge what does the water flow in through
Body Wall
What does the expression of proneural genes mean for a cell
It is competenet to become a neurone
What are the two roles ephrins and ephs play
Keeping axons out of specific area and compartmentalising the embryo into specific domains - e.g. rhombomeres
Mixture of neurones fasciulate wit
Their own kind
What class of receptor is TrkA
RTK
Describe gangliation
Coming together of many neurones into a cluster // allows communication between many neurones
What is the result of ectopic limb bud grafitng in the chick embryo during development
Increased survival of synapses and motor neurones in those regions
Give an example of how Euglena repsonds to a stimulus
Responds to light photons transduced by pigment localised to the eyespot
T or F: The posteiror nervous system develops as the involuted node regresses posteriorly down the primitive streak
T
Name an example of a segmented worm
Annelids
What sits under the anterior neural plate
Prechordal mesoderm
Describe the labelled pathway hypothesis
Axons selectively fasicualte with others due to the srufaces carrying cues. Different growth cones express different receptor sets for these cues. Early pioneer axons form a scaffold
Shh -/- causes
Multiple dysmorphology
Why is the NS ventral in insects but dorsal in vertebrates
Common ancestor: Ubilateria - rotation of head by 180 lead to one NS ventral, one dorsal
What three places do sensory neurones originate from
Neural crest, neural tube or placodes
How many neruones and glia are there in C.elegans
302 neurones // 56 Glia
What were Beckers experiements, what were his conclusions
Implanted sarcoms provoked selective survival of non-placodal sensory and sympathetic neurones. This demonstrates the presence of a diffusible gorwth factor, when antibodies were raised against the factor DRG growth blocked
What is the fate of the majority of the neural plate border cells
Express transcription factors and give rise to neural crest cells which migrate all over the body in turn giving rise to a vast number of cells
What do the anterior endeoder and prechordal mesoderm induce
Anterior neural transcription factors
Explain the Wiess resonance theory when trying to explain axon guidance
Cell body of the neurons sends out random and diffuse neuronal porjections to all targets followed by the elimination of non-functional connections
What type of cells were likely to be the first example of neurones
Sensorimotor cells
Where do neural crest cells which form the Symp/para ANS coalesce
Beneath the notochord and the aorta
What does the ventral nerve cord show evidence of
Gangiation and cephalisation
Are axon pathways hihgly steroetyped
Yes
t or F - Robo is expressed at high levels at all times in the commiusrelss mutatns
F - initially NOT expressed at high levels in the commisssural neurones it is only expressed at high levels once the axon has crossed the midline
What nerve cords do the nematode worms have
Dorsal ventral and lateral nerve cords
What experiement provided evidence for the organisers role in nerual induction
Speman and Mangold - Organiser graft
Neurogenic mutant
Too many neurones developing
At what end is FGF WNT AND RA highest
Posterior
What occurs when F-actin contracts
Cells forced to change shape on the apical edge causes the formation of the neural tube
What do Euglena show a response to
Light - photons transduced by pigment in the eyespot
What occurs on the ventral side in insects and worms
Sog and Screw exp, sog inhibits dpp binding to its receptor, cells take a neural fate, neurogenic region formed
What is different about the neural cells in Xenpous
Don’t delaminate and remain as one layer
How do we create tissue specific knockouts
Create a model system in which loxP sites have been introduce either side of the target knockout gene. Cross this organism with another that has cre recombinase (which works on loxP sites) under the control of a promoter which directs expression of genes only in the target tissue. Progeny produced with have a normally functiong target gene except in the target tissue
T or F the greater target tissue mass the more NT avaialble to a neuroen
T
Sum up delta notch
Initially both cells equally capable of making delta and receiving notch, change/bias introduced so that one cell begins to make more inhibitory signal than the other
Recall the Shh pathway
Shh is a signalling molecule which binds to and inhibits pathched which results in the repression of the inhibiton of smoothened by pathced. Smoothened then free signal resulting in the activation of Gli A and Gli R - Balance between the two forms
Proneural mutants
No development of any neurones
What is the primary fate of cells in the proneural cluster
Neuroblasts
Where would you typically find expression of BMP antagonists
On the dorsal side of the embryo
What transcription factor is induced in the NPB as a result of intermediate levels of BMP sig
MSX1
Segementation in drosophila controlled by
HOX genes
Do growth cones turn>
No they reoragnaise
Commissural sensory relay neurones are initially attracted to the floor plate of the developing neural tube but then once having corssed it they are repelled by the floor plate - what are the guidance cue molecuels involved in this phenomena
Netrins released by the floor plate initially act as chemoattractive guidance cues to direct axon growth toweard it, Once the axon crosses the midline it loses all sensitivity to netrins and becomes sensitive to inhibitory guidance cues in the form of semaphorins and slits expressed by the floor plate which repel axon gorwth away from it
What does the EMS cell give rise to
MS and E
What was Weiss theory
Resonance - random diffuse connections, non funct eliminated
Are myocytes neurones?
No
Where are interneurones in the hydra located
In a nerve net
What occurs at the same time as neuralation
Involution of the axial mesoderm (notochord and prechordal mesoderm form and come to lie benath the ventral midline of the nerual tube
How many of the 8 cells in the proneural cluster bcome neurones
1
Trunk neural crest cells that have migrate into the axial mesoderm differentiate into …
The dorsal root ganglion
What happens to radial glia nuclei in S –> G2
Nucleus moves away from the mantle towards to ventricular zone
In what order are the forebrain, midbrain and hindbrain formed
Forebrain first - then hindbrain and the midbrain forms last
What makes up the axial mesoderm
Anterior endoderm, pre-chrodal mesoderm and notochord
Do BMPs act as morphogens
BMPs from the surface ectoderm/roof plate act as morphogens to pattern other parts of the dorsal spinal cord
What does the neuroblast diff into
Ganglion mother cells and another neuroblasts
What does the axial mesoderm laid down in the wake of the posteriorly moving node induce
The proliferation and growth of the back end of the neural tube
What does less target give
Fewer synapses and neurones
What is the name give to the strucutre at which axon reporogramming occyrs
Choice point
What happens to commissural sensory relay neurones after they have crossed the midline of the hind brain
Lose their response to chemoattractive netrins
Describe distrib of SMAD1/7 on dorsal side
Low smad 1/ high smad 7 as BMP inhibited
What are hox genes activated by
Specific concentrations of posteiriorising facotrs
What does Shh cause in cells
Certain set of TFs confering ventral neural tube identities, set dep on conc of Shh cells is exposed to
What interaction induces mid brain strucutres
Interactions between hindbrain and forebrain
What is the vert homologue of SOG
Chordin
Notochord and FP become
Ventral
T or F - levels of FasII are able to influence the ammount of fasiculation in the ventral nerve cord of insects
T
In early devleopment a large number of synapses and nuerones are seen throughout the neuraxis with DRGS the same sixe throughout the body plan, how is this different in later development
At a later stage in dev DRGs at the limb regions are much larger than those at inter limb regions
Drosophila life cycle
0 days –> Egg // 1 day –> Hatching of the larva (3 stages) // 5 days –> Pupation // 9 days - Metamorphis produces the adult
How many neurones, how many connectiosn by each, how many connections total, how many genes, so how must genes be used
10^11 // 1000 ==> 10^14 // 20000 so must be used in combination
What is the name given to the posterior neural tube
Notochord
Layer three of the retina (furthest from the RPE cells)
Ganglion cells
What is the name of the molecules secreted by the floor plate directing axon gorwth toward it
Netrin
Descirbe RA signalling
Intracellular receptor when RA bound - enters nucleus and affects gene expression
What is the active subunit of NGF
B
Top end of neural plate bord crucual for
Head placodes
Where would GliA gdt be at its highest
Ventrally - more Shh
What does c-myc do
Induced ID –> proliferation and multipotency
Temporal axons go
Anterior
What can be said about the GliA GliR balance with Shh not bound
Higher levels of GliR
What is seen in a sema -/-
Several inappropriate axon projections rather than just innervating one target cell
What is the key difference between neuralation in vertebrates and innvertebrates
In invertbrates - indiiudal neuroblasts delmainate and froms neurones which cluster into a glanglia /// In vertebates the entire dorsal cell sheet is indcued to neural identity known as the nerual plate which rolles up to from the neural tube
What is seen when the limb bud is removed
Fewer DRG and motor neurones
What is the low affinity receptor for NGF
P75-NTR
What is the invert homologue of BMP1
Tolloid
Lower end of neural plate border crucial for
Neural crest formation
How does the neurogenic region arise
Through inhibition of the BMP/DPP signalling pathway
What have recent studies revelaed about Hydra
Have neurosecretory cells that secrete hormons
What cells does the body, muscle, gut and gonad give rise to
MS E C D
What are some examples of hormones secreted by neurosecretory cells of the Hydra
Insulin, somatostain, glucagon
What is the invert homologue of BMP4
DPP
Define commisures
The crossing of the midline to allow neurones to synapse with effects of the contralateral side of the body
What is the name of the strucutre that gives rise to the forebrain, midbrain, hindbrain and spinal cord?
Anterior posterior neuraxis
What occurs when growth cone restin, how does this change when growth cone encounters an attractive cue
Resting –> Tubulin dragged sporadically into the filopodia - this dragging occurs more frequently when growth cone encounters and attracte cue
What neurones form ventrally in the midbrain
Dopaminergic
T or F NGF is only important for the survival of neutrites
F - also imp for the survival of the soma and can guide gorwth cones in vivo
What classes of molecules lead to an induction of neural tissue that has an anteiror character
BMP and Wnt antagonists
Where can axons only gow
At places where they can adhere
What type of signalling exists between pairs of cells in a proneural cluster
Juxtacrine
What vesicles form the forebrain
tele and di
Which cells migrate and generate the parasympathetic ganglia
Vagal and sacral neural crest cells
What neurones form ventrally in the forebrain
Hypothalamic
How could you test to see if a morphogen is secreted from the notochord
Graft notochord in ectopic site of host embryo – should induce a secondary FP and secodnary set of motor neurones with bilateral symmetry
What neurones form ventrally in the hindbrain
Sertonergic
In the mature cerebellum how many climbing fibres synapse with each purkinje cell
1
What type of behaviours are found in more complex organisms
anticipatory
What is the TF crucial for development of the eye, what occurs if it ectopically activated
PAX6 leads to ectopic development of the eye
Signals from the notochord cause
Cells at the back end of the neural plate to proliferate and transform from anteiror to posteiror identity
What are the two properties of a basic nervous system
Receptive and responsive
Are posteriorising signals antagonised by prechordal tissue
Yes
Where is cephalisation seen in flat worms, segmented worms and insects>
Anterior/rostral end close to the pharynx
High SMAD1/low SMAD7 leads to expression of
MSX, GATA1 and other epidermalising transcription factors
Where are mature connections between prukinje fibres and climbing fibres made
In the dendrites
T/F Being recepting responsive and spontaneous Euglena show an example of a NS?
T
What are myocytes (sponge)
Specialised muscle cells that respond to strech
What occurs when TrkA is act
Ligand induced dimerisation and autophosphorylation… then has complex downstream pathways
Define fasculisation
Large bundles of axons in a fasicle instead of individual axons
What is the difference in acting arrangement in the structures of the growth cone
F-actin bundled together in a polarised fashion in filopodium whereas in the lamellae they are cross linked to form a net
Ear develops form the
ootic placode
Signals form the organiser inhibit BMP signalling to …
Dorsalise and pattern the adjacent mesoderm
What is the nerual plate border crucical for
Formation of the nerual crest cells and the PNS, formation of the roof plate and the closure and internalisation of the neural tube
What are climbing fibres an example of
Decreasing convergence in development
What is seen in ROBo mutants
Insensitivity to slit protein so all commissural neurones go back and forth across the midline forming roundabouts of neurones fourming ROUNDABOUTS. They are constnantly attracted to the Netrins produced by the midline glia cells and not repelled by the action of slit
Describe what occurs to express delta
Achatete scute proteins cause expression of delta which is recived by the notch receptor
Explain the actin treadmilling that is seen in the resting growth cone
F-actin subunits are added at the peripheral zone, move through the microfilament and are removed at the central zone. Tubulin is sporadically drageed into the filopodia
What happens during development of the lens placode
Thickening of ectoderm where it touches the optic, groove/vesicles, optic vesicles then invaginates to form a double layered cup
What cell fate is taken when BMP signalling antagonised
Neural identities
What are the simplest type of neurones found in Drosophila
Neuroblasts
What is seen in FasII mutants
Defasciculated axons
What is seen in delta notch -/- mutants `
All cells in the proneural cluster become neurones
What strucutre does the organiser differentiate into
Prechordal mesoderm and notochord
What is the roles of the roof plate cells
Important in the final step of neurulation and dorsal neural tube patterning
What TFs are activated by achaete and scute that are involved in specifying neuronal diff
Neurogenin
What is the effect of Chordin/SOG of BMP sig
Inhibition
Define lateral inhibition
Induction often used to make initally similar cells ifferent from one another
What casues neurones to fasiculate with only their own kind
Repulsive cues triggered when the neurones come into contact with each other enduces the collapse of the growth cone by destabilising the F actin between axons of differening neurones
What are rhombomeres
Regions of the hindbrain which form from the rhombencephalon
In chicks and humans the hollow sphere seen in Xenopus becomes
Flattened into 3 sheets
Where was NGF isolated from
Submandibular gland
T or F Differnet populations of neurones are affected by loss of different neurotrophin receptors
T
What are the main distinguishing features of a growth cone
Filopodia - long projections, lamellae -web like fanning between the projections
What does Shh bind to
Patched
Where is sShh secreted from
Notochord then FP
A multipotent progenitor can form either
A glial progentior or a comitted neural precurrsor
T or F - Commissureless is only expressed in the comissural neurones
T
From the results of the capenot expt what can be concluded about NGF
Affects cell and neutrite surivival and guides growth cones. Acts in a tropic and trophic manner
What class of recepotr is the recepotor which NGF binds to with hi affinity
RTK
What cells are involved in dorsal neural tube patterning/diff
Roof plate cell
Explain the projections seen in the retinotectal pathway
Connections are flipped - nasal neurones of the retina project to the posterior tectum, temporal neurone project to the anteiror tectum
What is the effect of BMP1/Tolloid on BMP sig
Increases
Describe myocytes before and after evolution
Originally act as an independent effector but then after evolution there is a sensorimotor neurone connection to the myocytes
How do Dpp and Sog (genes/products) interact in order for cells to adopt a nerual fate
SOG binds to dpp in the ECM and prevents it binding to receptors
What are the two daughters of the P0 cell
AB and P1
What is the role of PAX 3 6 7 and Lim1
Cause neural tube progenitors to acquire dorsal identities
Wnt acts with PAX3 and ZIC1 to express
C-Myc Id and Snail and Fox D3
What are radial glia thought of as, why?
Neural stem cells, provide a pool of undifferentiated cells that are used to build up the NS
How many neurones/glia in C.elegans
302 neurones // 56 Glia
Explain how comm, robo and slit interact in the invertebrate embryo
Slit binds to robo. Comm encodes a trafficking protein that prevents the vesicles containing robo reaching the cell surface or neurones therofroe preventing the inhibitory slit signal being received. After crossing the midlin comm expression turned off and robo containing vesicles reach the surface and the cell can respond to the slit inhibitory signal allowing it to change direction
Where would you expect to find the highest concentrations of BMP and Wnt in the developing neural tube
Dorsally
The neural plate border forms on the edges of
BMP singalling
What factors help determine which cell types neural progenitors differentiate into
Position or origin of neural crest cells, time of generation and migratory pathway
How do Euglena show aspects of possessing a nervous system
Exhibit sponataneous swimming and activity and respond to light
What is secreted by the nod
BMP antagonists
Describe the delta-notch signalling pathway
Elevation of notch signalling in one of the cells reuslts in an upregulation of suppressor of hairless and enhancer of split in that cell. SuH and Espl result in the downregulation of achaete and scute in that cell which in turn down regulates delta. In the other cell decreased activated notch receptors (due to dec delta in the original cell) results in a decrease in SuH and Espl expression in that cell meaning there is less inhibition of achaete and scute. With achate and scute signalling increased the cell expresses more delta, this cell will give rise to a neuron as achaete and scute transcriptionally activate neurogenin
Roughly when does a daughter cell decide on its fate in the devleoping NS
Immeidiatly after division
What were the Hydra recently found to have
Neurosecretory cells
Where is BMP action inhibited
In the dorsal of the embryo
T or F Permissive factors both define a substrates path and dictate the direction of axon growth
F - cant dictate direction
What is the drosophila homologue of SHH
Hh
Is retinoic acid an example of a morphogen?
yes
What process aloows both axons to stick to the scaffold but then also to get off when their target is reached
Control of fasciulation
Do lots of synapses fail during dev
Y
Explain how the midbrain is formed in the early embryo
Interaction at the border between the forebrain and the hindbrain results in an induction of midbrain like tissue
Sponge water in through
Body Wall
What does the suprapharyngeal gland form
Primitve brain
High levels of achatete scute in one cells …
Leads to production of BHLH protein and cell forms a neuronal precurrsor
What is the invert homologue of BMP7
Screw
T or F: Some all of the neural plate border cells form neural crest cell
False - some neural plat border cells are retained and form roof plate cells
What is the vert homlogue of tolloid
BMP1
3 domains of the growth cone
Central trans, and peripheral
What type of body symmetry is seen in worls
hydra are radially symmetrical and thus posees a nerve net rather than a central NS but without a brain or any type of cephalisation - this does however allow Hydra to respond to physical contact as well as detect food and other chemicals
What are the nerve cords of C.elegans
Ventral dorsal and lateral
Where is Shh highest
Ventrally
When are the ganglion cells of the retina born
Born first migrate last
What signalling pathway leads to the lateral inhibition in the proneural lcuster
Delta notch signalling pathway
What can be said about when the rods are bord
Born last migrate last
What causes the change in behaviour of axons crossing the midline in vertebrates
Robo3/Rig1 inhibits robo1 from acting until the axon crosses the midline
What type of induction is used in proneural clusters
Lateral inhibition
What arent neurotrophins abundant in the dev embryo
Because they specifiy reigonal areas of cell survival and dictate a selection process. Too many neurotrophins would result in too many neurones and synapses surviving
What is the name of the strucutre that forms at the ventral midline of the neural tube
Floor plate
Where is robo expressed
Expressed at high levels in the axons that don’t corss the midline
What was Sperrys theory
Chemoaffinity - directed and specific axon growth following identification tags
Where is chordin expressed
Dorsally
At the same time as genes that control survival, proliferation and multipotency, what other class of genes are turned on, what effect does this have
genes which promote epithelial-mesenchymal transition causes delamination of neural crest cells and they migrate away
What does extra target give
More synapses and neurones
What type of genes control segment identity
Homeobox containing genes (Hox)
What are the two recepotrs NGF binds to
TRKA and P75-NTR
What is the BMP/Wnt/Shh gradient converted into
GliA GliR gradient
What is a capenot chamber
Central chamber with two zones either side, thin gaps under the walls enough for axons to extend under but cell body cant get under
Low levels of achate scute in one cell …
Cells adopts the supporting cell fate
What are the two models for segmentation due to gradients
Alan turing reaction diffusion and Wolpert postitonal information
What is the high affinity NGF receptor
TrkA
What do the AB cells divide to give
ABA (L and R) ABP (L and R)
What is found in the inner layer of the optic cup
Contains a stem like population
Nasal axons go
Posteiror
What does the pre-chordal mesoderm form
Head
How is B NGF secreted
As a dimer
T or F: In the prospective hindbrain, BMP and Wnt inhibitors ensure that no posteiorising signals function
F - BMP and Wnt inhibitors prevent posteriorisation in the prospective forebrain
The levels of which gene product signalling is responsible for controlling the levels of SuH and Espl
Notch signalling
What type of force do semaphorins use
Contact repelllant
High levels of nodal gives the
Organiser
If the NPB cells are crucial for roofplate formation what must they also be imp in
Patterning of the dorsal neural tube
T or F Only some neurones can bind to P75-NTR due to its low affinity
F - all can because low affintiy
Which process results in the formation of neuroblasts and neuroectoderm from the proneural clusters
Lateral inhibition
Radial glia dividie asymm, what two cells are formed
One like mother, second uses the scaffold to migrate laterally and dif into a neurone
How do the BMP antagonists act
Bind with higher affinity to BMP receptors of bind directly to BMP altering its connfimation and preventing binding
Recall the features of neural inducers
Expressed by organiser, overexpresison in ectopic site leads to the induction of secondary axis, inhibition prevents the formation of the axis
What are the four forces of axon guidacne
Contact attract/repul chem attract/repul
What type of neurones do hydra contain
Interneurones and motor neurones
Example of a proneural mutant
Achaete scute mutant
What do the leading edge cells become
Anterior endoerm
Can neurones change which NT they require throughout development
Yes
What causes the formation of the neural plate border
Cells have received an intermediate level of BMP and have begun to go down - but not fully - a neural fate
Where is Ra highest
At the posteiror
What is spinobifida
Failure of the neural tube to close properly
During neuralation what happens to the mediolateral axis
D-V
What occurs when Shh is bound to ptc
Inhibition of the inhibition of Ptc to smoothened so free to signal to Gli
What is the name given to the anterior neural tube
Prechordal mesoderm and notochord
Is Shh only expressed in the hindbrain T/F?
False also expressed in the forebrain and the midbrain
Upregualtion of BMPS and WNTs byt the RP cause neural tube progenitors
to adopt dorsal identities
What does the nerual crest cells form
PNS, adrenal medulla, melanocytes, facial cartilage, dentin of the teeth
Example of a neurogenic mutant
Notch -/-
How do antagonists of BMP/DPP act, name two
Act as a sponge to mop up BMP4/DPP (making it unable to bind to receptor, competitive binding NOGGIN AND CHORDIN FOR BMP ::: SOG FOR DPP
What happens when NGF binds to recepotrs
It is internalised and transported to the soma via retrograde transport
What does homeobox DNA encode
A 60 AA DNA binding protein - homeodomain
Descitibe the lamella
F actin is bundled into a net
What are Hoxa1 and Hoxb1 required for
To specity rhombomeres 4 and 5
What is the morphogen secreted by the stucture at the ventral midline of the nerural tube
Sonic hedgehog
P1 gives rise to
EMS and P2
Name the earliest source of axon guidance cues
Pioneer axons - form an axon scaffold on which later axons are able to project
Neuroblasts are
Dividing progenitors
Layer two of the retina
Bipollar neurones
How are folate receptors involved in spinofifida
Folate receptors differentially expressed on the apical edge – folate binding causes constriciton – spinobifida linked to a decrease in folic acid
What are neurotrophins
Trophic factors for neurones
What is the main nerve in dropshila
Ventral nerve cord
Discuss the influence of laminin concentration on axon growth
Laminin concentration has no effect on the direction of growth although growth only occurs within a particular range on laminin concentrations
Where does neural plate induction occur
Where BMP signalling has become inhibited
What does SOG stand for
Short gastrulation
When does neural crest formation occur
During neuralation
Without Shh bound what is the function of patched
To inhibit smoothened
The expression of which two TFS involved in detla-notvh leads to the downregualtion of achaete and scute
Enhancer of split and suppressor of hairless
What experiment can be used to for evidence of Shh – what were the reuslts
Bead soaked in purified Shh is able to mimic the notochord - induces secondary FP and ventral motor neurones with bilateral symmetry
What do GMCs form
Neurones and glia
What occurs if NGF is only present in the central chamber
Cell bodies survive but axons die and retract
On the ventral side (insects and worms)
Cell fate takes a nerual cell fate and Sog prevents dpp from binding to its receptor - this forms a NEUROGENIC REGION ON THE VENTRAL SIDE
Describe the distribution of Smad 7 and 1 ventrally
BMP signalling ==> high SMAD1 and low SMAD7
What is meant by delamination
In C.elegans the neural cells migrate into the blastoderm from the surface ectoderm
What to growth cones require to grow on
Permissive ubstrates
Which gene network dictates dorsal and ventral sides of the body in insects and worms and are responsible for the developing neural regions
Dpp-SOG network
What two unusual phenotypes are seen in genetic screens in drosophila that exhibit problems with the neurones of the ventral nerve cord
Roundabout mutants - no longitudinal neurones becasuse of robo mutation and commissureless mutants - show no neurones crosseing the midline due to a mutation in comm
What 3 molecules secreted by Speman organiser, what does this cause
Chordin noggin and follistatin inhibits BMPs signalling inducing a neural cell fate
T or F early in development only a single axon innervates a muscle fibre and this is maintained despite increasing numbers of neurones throughout the course of development
F - initially many neurones innverate this decreases to a single later in dev
Recall the inhibitory molecules released by the floor plate that contribute to the guiding of commissural releay neurones after they have corss the midline of the spinal cord
Semaphorins and slits
What is the low affinity receptor for NGF
P75-NTR
What is te vert homologue of Screw
BMP7
Describe B-NGF
Is a dimer and the active component of NGF so works alone
What is the name of the vertebrate homologue of dpp
BMP4
What can be said about the GliA GliR balance with Shh bound
More GliA than GliR
Explain interkinetic nuclear migration
During G1 and S phase the cell bodt is at the mantle but during M phase and cytokinesis the lateral attachement to the plial surface to the plial surface is lost and then reforms
What would be seen if development was halted at the instant the prechordal mesoderm has just involuted
Can see neural plate expresses markers that are later confined to the forebrain - early neural plate is anterior in character
Where in the early stages of development are most of the synaptic connections made
Soma
What class of molecules released from the organiser induce neural plate formation
BMP antagonists
What is the invert homologue of Chordin
Short gastrulation (SOG)
What structures does the nerual plate border give rise to
Peripheral nervous system and the roof plate cells
What happens when a growth cone comes into contact with an attractive cue
F-actin treadmillings slows down and F actin begins to accumulate which stabilises the filopodia. A molecular clutch engages the extension over the substrate and an actin-tubulin link pulls the microtubules into the wake of the extedning filopodium
Where do neural cells form
Where Dpp is inhibited by SOG
What reg water flow in sponges
Myocytes
What does fasciciulation involve
Homophilic binding by cell adhesion molecules
T or F - Water enters the sponge through the soculum, flows through the organsism controlled by flagella and the leaves through the body wall
False - water enters through the body and leaves through the osculum
What does the Ra gdt induce
Different patterns of hox transcript
What cell gives rise to the germ line
P4
Early neuroepithelial cells dif
Symm
Main advanatage of C.elegans
Entire NS mapper
Give some examples of the multiple dysmorphology seen in Shh k/os
No vent of the neural tibe, holoprosencephaly, cyclopia, abnormal limbs/digits and lack of a pituitary gland
What is seen in Comm mutatns
Robo protein is expressed in all cells that would normally but which now project their axons longitudinal
Inhibitiory guidance cues can be either
Membrane bound or secretory
T or F pioneer axons establish an axons scaffold on which follower axons later project
T
What is dorsal character achieved through
Shh repression
Name three other familes of survival factors ther than neurotrophins
Cytokines, glialderived growth factors and testosteron
What two components occur the allow the filopodium to extend
Actin-myosin based actin tubulin link pulls microtubles into the wake of extending filopodia —- Two molecular clutch engages to slow rearward actin treadmilling
5 charactreristics of a worm
Gangliation, cephalisation, bilat symm, fasiculation, and comissures
What is the hierarchy of the visual system anatomy
Object - lens - retina - tectum
What two types of cells do neuroepithelium in the ventricular zone give rise to
Neurones that move laterally, radial glia retained at the VZ and these extend lateral projections to the plial surface
In a sponge what does the water flow out through
Osculum
What are the effects of FassII overexpression of defasciculation
Motor axons fail to defasiculate (get offf the scafofld) so they miss their targets
In vert - k/o of Robo1 leads to a phenotype similar to which other k/o
Netrin -/-
Do segmented and non segmented worms show cephalisation
Yes
Where would the GliR gdt be at its highest
Dorsally - where Shh gradient is lowest
The neural crest is sometimes referred to as the 4th germ layer … names some of the cell types it differentiates into
PNS cells, adrenaline producing cells of the adrenal gland, pigment containing cells and skeletal and connective tissue of the head
Notch-delta what Is the receptor
Notch
What is the clustering of neurones around the pharynx called
Suprapharyngeal ganglia
What was proposed in 1948 by Becker
Fast growing muscle cells may secrete survival factors
Which gene product in this lateral inhibitior pathway acts as the inhibitory signal and directs cells to their primary fate
Delta notch signalling pathway
What does Shh govern
Ventralisation along the whole rostro-caudal axis
What does TrkA affect
Differentiation, growth and movement
What expeirment was used to analyse NGF function
Capenot chamber with NGF in all chambers vs NGF in only the central chamber
What two methods can be used to visualise the 3 germ layers
In situ hybridisation or AB stain
Define cephalisation//how does it help
Emergence of differences between the head and tail end // allows for more complex neurones around the mouth - useful for fedding
What do HOX genes specifty
A region of the AP axis
What can be said about the organiser as it self-differentiates with regards to its position
It involutes and extends underneath the induced neural plate
Where is one place cues can be found
On other axons - i.e. one making a turn when it encounters another axon
Explain Sperrys chemoaffinity hypothesis
Neurones undergo directed and specific outgrow through axons following individual identificaiton tgas
When two neurones fire at the same time what occurs to the connection
Becomes stronger
Two basic properites of a NS
Receptive and responsive
Upreg of BMPs and WNTs causes expression of what TFs
PAX 3 / 6 / 7…….. LIM1
During neuralation what happens to the mediolateral axis
Becomes the dorsoventral axis
What is the high affinity NGF receptor
TRKA
What type of axon is guided by the floor plate
Commissural sensory relay neurones
How do we overcome the problem of having 20’000 genes yet 10^14 connections to make
Genes must be usd in combination
What determines where the 3 germ layers form
Early on gravity causes separation of various cytoplasmic components
What happens to radial glia nuceli in M
Nucleus at the VZ and attachement to mantle lost
The organiser secretes BMP antagonists what transcription factor controlls this
GSC
What inhib guidance cue family are responsible for the collapse of differening growth cones
Semaphorins
Why must the image be flipped in the tectum
Flipped once from the lens to the retina so must be flipped back
What is the invertrbate homologue of BMP7
Screw
6 cell movments during embryogenesis
Invagination, involution, ingression, delamination, epiboly and convergent extension
What do the radial glia nuclei go through
Interkinetic migration
How many Drosophila larval stages
3
Give some examples of posteriorising signals
Wnt, FGF and retinoic acid
What subunits of NGF are involved with storage
Alpha and gamma
Can growth cones turn
No they reoragnaise
What is the name of the first discovered neurotrophin
Nerve growth factor
What is seen from a in-situ hybrid of Shh mRNA
Initially expressed by the notochord … then expressed by the floor plate cells
What happens for Ti1 –> Cx1 if last signpost ablated
Growth cone stalls and doesn’t make the last medial tuns
What is the result of Shh signalling in progenitor cells
Induces the expression of TFs that confer ventral nerural tube identitites and ultimately result in the differentiation of those cells into ventral neurones
Contact between two neurones of different timp leads to
Collapse of the growth cone
Where are WNTS and FGFS expressed (NPB)
Preaxial mesoderm and the non-nerual ectoderm
How do radial glia divide
Asymmetrically
T or F All animals requires NTs at some point in development
F - drosophila and C.elegans don’t
What occurs on the the dorsal side in insects and worms
DPP, Tld, Tsg, CV-2 expression, no inhib of DPP, cells take epidermal fate
Does the regrowth of nasal retinal axons to the correct tectal location (posterior) show that axons are guided by specific cues during development
No - because axons growing over exisiting debris during a regeneration - cant be assumed to be the case in development as well
What is found in the outer layer of the optic cup
RPE –> produces melanin
Where is BMP4/7 expessed
Ventrally
Expression of NeuroD commits cells to
Neural cell fate
What are the names of proneural genes being expressed in the proneural cluster and are also needed for the expression of delta
Archatete, scute
Neurogenic regions in Xenopus is
Next to the skin
What is seen when commissural sensory relay neurones have crossed the midline in the spinal cord
Crossed –> they turn because they lose senstivety to chemoattractive netrins but gain sens to chemorepulsive molecules released by the floor plate
Pax3 and Zic 1 are known as
Intrinsic transcription factores
What is seen on the apical side of cells of the neural plate
Bands on F-actin
What Is the effect of removal of a chick limb bud on the development of the nervous system
Removal of a limb bund = fewer MN and synapses in the regions where the limb bud was removed … this is due to higher levels of cell death
To which cells do the climbing fibres of the cerebellum project to
Purkinje neurones
Recall some of the of the BMP antagonists expressed in the dorsal side of the Xenopus embryo
Noggin, Chordin and Cb
T or F are differnet combinations of neurotrophins required for the survival of different neurones
T
Neural crest cells can be thought of as the
4th germ layer
How many layers of the optic cup
2
What is seen as a result of FasII overepxression
Novel/overfasciculatio
What is the name given to cells that control water flow in sponges
Myocytes
What are the two types of neurones seen in the ventral nerve cord of drosophila
Commissural and longitudinal
Notch delta what is the ligand
Delta
How are different domains of the hind brain determined
Specific hox gene signitiutre
In the devleoping drosophila ventral nerve cord you can oserve commissural and longitudinal neurones, what factor is being secreted by midline glia cells
Netrins
What does explou2, soxD exp lead to
Exp of neurogenin
Recall Sperrys 1963 experiment
Cut the optic nerve and removed temporal retina allowing only nasal axons to grow back
How is asymmetrical division achieve
But polarisation of cytoplasmic determinants
What happens if comm expression is force in all the neurons in the ventral nerve cord of the dropsophila
Robo protein expression is lost everywhere resulting in the Robo mutant phenotype
What was seen in the Speman mangold organiser graft
Secondary neural tube - host derived SHOWS… whilst axial mesoder were donor derived SHOWS…
In worms and insects, neural precursors induced in one part of the body migrate inwards from the surface later in development - what is this process called
Delamination
An antibody stain of Shh reveals …
Shh expressed in a gradient and acts as a morphogen
What happens if part of the subplate ablated before axons extend
LGN innervation fails in the ablated region
P3 gives rise to
D and P4
Where does the Hensons node form
Tip of the primitive streak
What tissue is the neuronal cells in hydra derived from
Skin ectoderm
Where are SOG and SCREW expressed
Ventrally
What are rproneural clusters
Clusters of cells which have proneural genes activated so are competent to become neurones
3 antagonists of the BMP pathway
Chordin noggin and follistatin
The nerves in Hydra are distriubyted in a
Nerve net
P2 gives rise to
C and P3
Does the neural tube form under the influence of BMP
No - forms under the influence of BMP antagonists
Describe myocytes
Spec muscle cells which respond to strech
T or F : Although growth cones adhere better to collagen than laminin, they grow more on laminin
T
Layer one of on the retina (closest to RPE)
Rods and cones
What does arrival of the neurone at the target often coinside with
New expresison of a neurotrphin by the target
Define neurotropic
A factor that dictates direciton of neuronal growth
Describe the major features of the adult Drosophila nervous system
Bristle socket - consist of a sensory hair cell,a socket cell, a sheath cell and a sensory neurone
BMPS and WNTS released by the roof plate cells diffuse into dorsal neural tube and induce expression of which set of transcription facotrs
Pax6, 7, 3 and Lim1
What are neural precurssors
Cells that are able to give rise to any neuronal derievd cell
What sits under the posterior neural plate
Notochord
Where did becker purify the factor from
Snake venom and mouse submaxillary gland
What was seen when the optic nerve was cut and temporal retina ablated
Nasal axons grew back in the right place to the posterior and ignored area occupied usually by temporal
Describe the treadmilling of F-actin when an attractive cue is encountered
Treadmilling of F-actin and F-actin accumulates
What happens to the remaining neural plate border cells
Don’t migrate and form roof plate cells expressing BMP and Wnt morphogens in dorsal half of the embryo
What is the nerualplate border
Region between the neural plate and the non-neural ectoderm
What are two experiments that could be used to prove a moleucle is a neural induced
Overexp in ectopic site induces a secondary axis to form – inhibition of activtiy (k/o or antag) should prevent formation of an axis
How do neuroepithelial cells divide
Symmetrically generating two identical daughters
What does P75-NtR promote
Cell death or survival
T or F : Growth cones can be kept out of where they arent supposed to grow by contact repulsive factors
T
Describe the filopodium
Polarised F actin able to form larger bundles
Where do sub-plate neurones usually project prior to innervation of cortex by LGN
Cortex–> thalamus
What are the three other main neurotrophins that have been found
Brain derived neruotrophic facotr (BDNF) NT3 and NT4/5
What do the daughters of the radial glia cells become
One remains as a rdail glia (stem) cell, the other differentiates into a neurone and migrates laterally along the projection of the radial glia
How many HOX clusters in humans
Four
What does the accumulation of F actin cause
Stab of the filopodia dragging microtubules into the back of the filopodium
When a growth promoting cue is encountered two key components lead to filopodal extension, what are they
A molecular clutch engages and rearward actin treadmilling slows. Next the actin-tubulin link pulls the microtubules into the extedning filopodium
What is the homologue of Chordin
SOG
What transcription factors upregulated by NBP and Wnt cause proliferation and multipotency and characterise the neural crest cells
C-Myc Id and Snail
What is expressed at the posterior NP
WNT and BMP antganosists
Explain how we can see the decreasing innervation in skeletal muscle throughout development
Gradually increase stimulation of the afferents innervatiing a target muscle and record the post synaptic poteneint until max response reached. Rep throughout dev and a dec in max response will be seen indicating a decrease in innervation by the afferents
Define neurotrophich
A factor that promotes/feeds neurones
T or F Permissive and non-permissve factors can tell a growth cone which direction to grow in
F - They provide directional information
What vesicles form the midbrain
Mes
T or F: BMPS from the surface ectoderm/roof plate act as local morphogens to pattern other parts of the dorsal spinal cord
False! They induce expression in cells of the roof plate in the dorsal spinal cord
ON the dorsal side (insects and worms)
No inhibtion of the dpp pathway (antagonists not ecpressed) so cells take an epidermal cell fate
What occurs if NGF is present in all of the chambers
Cell is OK
What is the name to the equivilant organiser structure found in Gallus gallus embryo
Hensons node
What is the effect of sox9
Causes expression of Snail which inhibits cells death and promotes cell survival
What are the characterisitcs of the Vert NS
All have common body plan : Early NS similar across families, devlops on the dorsal side from the neural plate
What converts electrical activity into neuronal survival
More active a synapse the more NT it takes up so more likely it is to survive
Where is DPP expressed
Dorsally
What is the secondary fate of cells in the proneural cluster
Epidermis
At the nerual plate border what signals does MSX1 work with to turn on other TFs
WNTS and FGFs
Can neurones synth NTs or is it just the targets
T
T or F - Comm is a transcriptional regulatory protein
F - commissureless is a post transcriptional control protein
Low levels of nodal give
Ventral mesoderm
FP cells cause
Neurones to develop with bilateral symetry
What name of synapses that discovered the first neurotrophin
Hamburger and Monalcine
What cell do most of the neurones in the nematod worms derive from
AB cells
What is the Louis Wolpert positional information model also known as
French flag model
What happens when delta binds to notch
Suppressor of hairless leads to enhancer of split proteins which inhibits achatete scute proteins (so less delta made)
What does HOX stand for
Homeobox containing genes (Hox)
What is the name of a group of cells that have equal potential
Equvivlance group
What happens to radial glia nuclei in G1 –> S
Nucleus can be seen moving away from the ventricular zone
3 examples of cells in the dorsal neural tube with dorsal identities
RP, neural crst, dorsal sensory internueones D1-3
What is the effect of BMP4/Dpp
Expression on NON neural homeobox genes
What is the primary determinant of neuroaly/synaptic surival
Electrical activity post pre and post synaptically
What does low SMAD1 high SMAD 7 lead to
Exp of Xlpou2, soxD and other neuralising transcription factors
Where are MBMPS secreted from
Roof plate
what evidence is there to suggest there are growth cones located on axons
Expt in grasshopper embryo - ablation of 1 of 5 neurones results in change in projection of another axon in the nerve tract this is not seen in ablation of the other neurones proves that cue on the originally ablated neurone influences the guidance of the other neurone
How does the Shh gradient form a cartesian grid of information
Intersects the AP HOX gradient
What is the vert homologue of DPP
BMP4
What three types of cells differentiate dorsally
Roof plate cells neural crest and dorsal sensory neurones
Does the NS in Hydra allow them to detect the soruce of a stimulus
No - they cant detect the source
T or F there is no comm homologue in vertebrates but there are 3 robo homologues
T
What type of signalling is involved in the extension and posteririosation of the NP
RA signalling
T/F cells inhibted by BMP antagonists will go onto inudced formation of the neural plate
True
What can chemorepellants induce
Collapse of the growth cone
Neural crest cells are capable of giving rise to which cells
Neurones and glia
What vesicles form the hidng brain
Met myelen
What is water flow in a sponge regulated by
Myocytes
T or F Semaphorins are permissive factors
F - non permissive
What is the name of the strucutre in the Xenopus embryo that express transcription factors that lead to the expression of BMP antagonists in the dorsal side of the embryo
Spemanns Organiser
True or False: The early border begins to epxress msx which acts with Wnt and FGF to turn on transcription factors Pax3, Zic1 and Pax7
True
Ectoderm and RP become
Dorsal
What occurs to the nerual crest cells to form the DRG
At posterior of sominte they are forced into the anterior by pissoffin which forms the bipolar neurones of the DRG
What is the role of robo
Cell surface receptor for the inhibitory proteisn slit
What is the name of the border that forms at the neural/ectoderm border
Neural plate border
Which of the two strucutres formed by the organiser is located most anteriorly and which is most posteiror
Notochord - posterior and prechordal mesoderm is anterior
Where in the neural tube is Shh expressed
Notochord and the FP
What superfamily are BMPs a member of
TGF-B
What are two features of a molecule is a neural inducer
Expressed in the organiser – must be secreted and act on adjacent cells
What do the ABA and ABP cells form
Hypodermis and the nervous system
What cell types do the nerual plate border cells form
Neural crest cells
In flatworms what is the suprapharyngeal ganglia intimately associated with
Mouth
What cells types can cells in the inner layer of the optic cup diff. into
Diverse ganglion cells, internuerones and light sensitive photoreceptive cells
What subunits is NGF
2 a 1 b 2 gamma
What is the other name for contact repellent substreate
Non permisive substrates
Define bilateral symmetry // what does it allow
Symmetry around the AP aixs - movement
What was the adult female Xenopus used for
Pregnancy test –> exposed to high progestoerone levels (as in preg womens urine) caused ovulation
How many primary brain vesciles
3 Pro Mes Rhomb
What is secreted by the notochord and then the FP
Shh
Sponge water out through
Osculum
After gastrulation all of the the regions of axial mesoderm will continue to make BMP and Wnt inhibitors
False - only the bits of axial mesoderm that involuted first will make BMP and Wnt inhibitors
What was proposed by Cajal about the growth cone
Growing tip of axon able to sense guidance cues
What phenomena does the growth cone exhibit that adds the number of different connections it can make without increaseing the number of genes
Changes in sens to different molecules
T or F commissureless is expressed before and after crossing the midline
F - only before
Why is the C.elegans a useful model system
Entire NS mapped
Describe the nervous system seen in flatworms
Two nerve cords, one on each side of the body, gangliation,cephalisation and faciulisation seen at the anteiror/rostral end // Commissures allow coordeination of both of the sides of the body
What two genes are turned on at the neural plate border ONE by WNT and FGF TWO by FGF
1) Pax3 2) Zic1 (only FGF)
What is the name of the non-permissve factor found on the cell surface and its receptor that are used early in patternirnig as well as later to guide axons and show reciprocal expression in the mammalian embryo
Ephrins and ephs
T or F Axons can use non-permissive factors alone to gorw and reach the target cell
F- they rely on a balance with permissive as well
Where is the [SHH] highest
Ventral neural tube
What was seen when T7-LS3 was cut out and reversed
Normal innervation, motor axons still find their way to targets, suggest axons can navigate
What is the homologue of Tolloid
BMP1
What signals are upreg by the RP cells
BMPS and WNTS
Neurogenic expression leads to
NeuroD exp
What is meant by the activation-transformation model
Neural inducing molecules initially released from early organiser cells induce and maitain the anterior/forebrain tissue. These molecules are only maintained in the prechord tissue once the organiser has differentiated. Other signals thus transform some of the prechord tissue into a more posteiror fate
What is seen upon addition of a limb bud
More DRG and motor neurones
