Brain development Flashcards
Neuraxis
Establishes interior, posterior dimension of the NS
3 stages of embryonic development
- cleavage
- gastrulation
- organogenesis
cell at day 4
Morula
solid ball of cells formed as the zygote undergoes cleavage
cell at day 6
Early blastocyst
hollow ball of cells with fluid filled cavity
cell at day 10
late blastocyst
pre embryo
embryonic disk
2 layers of cells that become the embryo proper
cell at day 16
embryo with 3 primary germ layers
ectoderm
mesoderm
endoderm
name of 3 cells in development
zygote
blastula
gastrula
ectoderm of gastrula and examples
outer layer
epidermal cells of skin
neuron of brain
pigment cell
mesoderm of gastrula and examples
middle layer
notochord
bone tissue
tubules cell of the kidney
red blood cells
facial muscle
endoderm of gastrula and examples
stomach cell
thyroid cell
lung cell (alveolar)
germ cells
sperm and egg
cleavage
Cleavage: rapid, multiple rounds of mitotic cell division where the overall size of the embryo does not increase. The developing embryos is called a blastula following completion of cleavage.
gastrulation
Gastrulation: the dramatic rearrangement (movement) of cells in the blastula to create the embryonic tissue layers. These tissue layers will go on to produce the tissues and organs of the adult animal.
organogenesis
Organogenesis: the process of organ and issue formation via cell division and differentiation.
how do stem cells decide which layer they belong to
stem cells - migrate to one of 3 layers
according to specific transcription factors
form gastrula in organogenesis
neural tube structure
center ->
1. archenteron
2. endoderm
3. mesoderm
(NOTOCHORD)
4. ectoderm
(NEURAl FOLD)
(NEURAL PLATE)
what is the neural tube
This neural tube serves as the embryonic brain and spinal cord, the central nervous system.
Neural tube formation steps
(1) formation of the neural plate;
(2) shaping of the neural plate;
(3) bending of the neural plate to form the neural groove
(4) closure of the neural groove to form the neural tube.
when does neural tube formation happen
It starts during the 3rd and 4th week of gestation
formation of neuronal tube explained
neural crest cells form in the region that connects the neural tube and epidermis
neural plate formes
edges thicken and move upwards to form neural folds
U shaped neural groove forms
neural folds migrate to middle of embryo
they fuse to form the neural tube beneath the overlying ectoderm
which end of neural tube become brain and spinal cord
anterior end = brain
posterior end = SC
after 4th week of development
how do malformations of the neural tube formation and name examples
NTDs occur when the neural tube does not close properly. The neural tube forms the early brain and spine.
e.g anencephaly
craniorachischisis
spina bifida
encephalocele
iniencephaly
spina bifida
spinal cord defect
anencephaly
brain defect
absence of the brain and cranial vault, without skin covering
Trans amniotic stem cell therapy
taking the trans amniotic stem cells and inject them into the utero into the embryo - starts the regeneration of tissue again and let the fusion of the neural tube be complete
transcription factors in brain development
BMP
FGF
Wnt
RA
explain stages of embryonic development
- morula = solid ball of cells formed as zygote undergoes cleavage
- early blastocyte = hollow ball of cells with a fluid filled cavity
- late blastocyte = pre eymbro = embryonic disk = 2 layers of cells
- gastrula = embryo with 3 primary germ layers
what are the 3 primary germ layers
ectoderm
mesoderm
endoderm
where does the neural tube lie
above notochord and mesoderm and below ectoderm
at how many days does the neural tube become brain and SC
at day 25 (4th week)
anterior end will double up into brain
posterior end = SC
how do cells decide where they belong along the neural tube
Gradient of retinoid acid
to understand what’s more rostral and what’s more caudal
is the spinal cord rostral for caudal
caudal
what is the role of FGF and GDF11
Oppose the action of RA and allow specification of the SC
what is inhibited to form the neural tube
BMP ( bone morphogenetic proteins)
Explain the formation of the embryonic CNS using transcription factors
- Blastocyst
- Ectoderm
activated by Ant and FGF
inhibits BMP4 using Noggin Chords Follistatin - Neuroectoderm
RA (generated by activation of RalDH2)
FGF and GDF11 ( oppose the activity of RA allowing specification of SC) - Neural Tube
- brain = rostral
-SC = caudal - embryonic CNS
what transcription factor control rostral activity
RA (Brain)
what transcription factors control caudal activity
FGF and GDF11 (SC)
What transcription factors posterise the neural axis
Wnt, FGF and RA
What is involved in anteriorising cells
Tlc
Cerbrus
Dickkopf
How is neural plate anteriorised
Cerberus and Dickkopf inhibit Wnt and BMP
Later TLC inhibits Wnt
to anteriorise the neural tube
function of TLC
inhibits wnt to anteriorise the neural tube and form telecephalon and diencephalon
What are the 3 parts formed from neural plate
forebrain
midbrain
hindbrain
what are the 7 segments of hindbrain called
rhombomeres
function of rhombomeres
vital functions
breathing and HR
cranial nerves originate
what do neural crest cells migrate to form
peripheral NS
melanocytes
chondrocytes
smooth muscle
what causes cells to migrate to specific areas
HOX genes
how do HOX genes influence neural crest migration
The cell will migrate into a certain area according to the amount the HOX genes are expressed, and which genes are expressed.
explain the patterns of neural crest cells in the forebrain, midbrain and hindbrain
Forebrain = neural crest cells travel as sheets
Midbrain = move as streams
Hind brain = move in segments
neuron pathways in rhombomers
motor or sensory neuron pathways
cholinergic or dopaminergic neurons
how are rhombomeres organised
HOX gene expression and is highly conserved
2 axis
anterior posterior
And
Ventral dorsal
2 axis
anterior posterior
and
ventral dorsal
how is the brainstem divided
into rhombomeres defined anatomicaly by physical segmentation
axis associated with rhombomere development
rostral caudal
If spine was divided in half what is the dorsal and what is the ventral responsible for
dorsal (somatosensory/afferent system)
ventral (efferent system)
what is restricted to specific rhobomeres and examples
cranial nerve nuclei
cochlea nevre
Vegas nerve
what gene is Associated with the specification of dorsal ventral axis
Shh
how are dorsal side and ventral side formed
dorsal side = BMP transcription secreted by upward ectoderm
ventral side = Shh secreted by notochord
what causes cells to go to ventral side
Shh secreted by notochord
what causes cells to go to Dorsal side
BMP transcription secreted by upward ectoderm
what does notochord release
genes required for development of midline structure
what is responsible for sensory neurons
BMP and Wnt
Diffuse as development takes place on ventral side
what transcription factors are most important for ventral dorsal axis
Shh and BMP
what is specifically associated to the transcription factor
progenitor domains
differentiated by their expressions of transcription factors
Give an example of a progenitor domain and the neurotransmitters involved?
P1 migrate to the V1 cell, which express TF En1, and will be an inhibitory neurone secreting GABA.
name progenitor domains
p0,p1,p2,pMN,p3
name post mitotic neuron types
V0,V1,V2, MN,V3
what determines the identity of ventricle spinal neurons
molecular code
go from progenitor cells to post mitotic cells
Progenitor domains characterised by their differential expressions fo transcription factors = migrate laterally here and then change name = transmitters
p0-p3 -> v0-v3
what is most ventral p0-p3
p3
what is needed to form connections
long distances
growth cones
microtubules (stable and dynamic)
actin
axon guidance
name of the cellular process involved in the progression of neural circuit
Axon Guidance
explain the repulsive mechanism of axon guidance
negative cues
repulsive ligand like cytotoxic
act through receptors
trigger the collapse of the cytoskeleton
so that cells do not grow in the direction
explain attractive mechanisms when forming connections
Receptors for positive cues (specific Tfs) to promote polymerisation of the cytoskeleton towards that side of the growth cone.
how does a neuron know what direction to form connections
axon guidance
attractive and repulsive mechanisms
what is ipsilateral growth of axons
On the same side
cytoskeleton proteins
stabe mT, dynamic MT and F actin
what axons grow longitudinally
Axons expressing Robo
Repelled by Slit
Grow longitudinally
what axons are attracted to the midline
Axons with low ROBO expression = attracted to the midline and cross over
what happens when axons cross midline
axons up regulate robot and remain on contralateral side
what is a neuromere
where the region in which the axon crosses = might have cross projection = different projections run ipselateral or become contrilateral
what is a neuromere
where the region in which the axon crosses = might have cross projection = different projections run ipselateral or become contrilateral
what model has ben crucial in uncovering fundamental mechanisms of neural circuit development
drosophila CNS
what receptor do peripheral nerves rely on to reach the periphery
neuropilin receptor
what ligand to the NRP1 receptor
Sema3A
What ligand to the NRP2 receptor?
Sema3F
what happens is NRP1 is knocked out
nerve do not reach the periphery
neural plasticity
ability of the brain to change structurally and chemically in response to experience
4 key elements of a complex variable enriched environment
cognitive
sensory
motor
social
How does plasticity change with age
Plasticity decreases
2 studies on language pathologies
RH crowding effects
Functional redundancy
plasticity in neurochemcial systems
cyclin or developmental change in expressed neurotransmitters
plasticity of cell assemblies and connection s
change in patterns of brain connectivity in response to endogenous input to input from the environment
plasticity in behaviour
change in strategy or approach to problem solving
functional redundancy
multiple langage specific neural systems
one is lost there are others to mediate language
what are the main subtractive events that play a role in development
neural cell death and loss of synapses
establish patterns of brain activity that are more stable
what plays a role in development and plasticity
genes and enviornmens = providing the input for proper developments
