Early Brain Development Flashcards
What is the human analog of dpp (decapentaplegic)?
Bone morphogenetic protein (BMP)
What is the organizer in humans?
Notochord
What does the notochord secrete that is important for neural plate formation?
BMP inhibitors:
- chordin
- noggin
- follistatin
What are the 3 flexures of the neural tube? Which are the first 2 that are formed?
- cervical flexure
- cephalic flexure
- pontine flexure
Cervial and cephalic flexures are formed first
What are the 3 primary brain vesicles?
Prosencephalon
Mesencephalon
Rhombencephalon
What are the 5 secondary brain vesicles?
Telencephalon Diencephalon Mesencephalon Metencephalon Myelencephalon
Which secondary brain vesicle becomes the cerebellum?
Myelencephalon
Which secondary brain vesicles form most of the brain?
Telencephalon and diencephalon
What is regionalization?
Development of the 5 secondary brain vesicles that eventually form the brain and spinal cord
What kind of fluid is located with in the primary and secondary brain vesicles?
Cerebral spinal fluid (CSF)
List 2 functions of the CSF
- protects against injury + gravity
2. homeostasis
Where is CSF produced?
Choroid plexus
What is the choroid plexus?
A mesh of blood vessels
Name a method for extracting CSF
Lumbar puncture aka. spinal tap
List 3 things that recovering CSF can diagnose
- CNS inflammation
- hemorrhage
- meningitis
What is CSF used to screen for?
proteins
glucose
pressure
List 2 disorders that result from improper sealing of the neural tube
Anencephaly (cerebrum and forebrain missing)
Spina bifida
List a disorder that results from abnormal development of the brain ventricles
Hydrocephaly
Which disease may be classified into non-communicating and communicating?
Hydrocephaly
What is hydrocephaly?
Build up of CSF within the brain ventricles
List 3 causes of hydrocephaly
- CSF reuptake inhibited
- excessive CSF production
- CSF flow restricted by abnormal ventricle development
What divides the spinal cord from the brain vesicles?
Foramen magnum
List 3 posterior signals
Retinoic acid
Wint
FGF (fibroblast growth factor)
Where is the isthmic constriction located?
Junction bw mesencephalon and rhombencephalon.
Binding of FGF8 to its receptor induces expression of a TF called:
engrailed (En)
Which 2 signalling molecules are responsible for establishing the dorsal-ventral axis of the spinal cord?
Shh (sonic hedgehog)
BMP (bone morphogenic protein)
Which body axis does Shh establish?
Ventral
Which structures produce Shh?
Floorplate
notochord
Which body axis does BMP establish?
Dorsal
Which structures produce BMP?
ectoderm
roofplate
Shh is a ___ protein
a) transmembrane
b) secreted
b) secreted
Shh is produced from the ___ which causes the ___ to then also secrete Shh.
Notochord, floorplate
T or F: Shh is necessary and sufficient for specification of ventral cell types
T
The ___ receptor (unbound) inhibits expression of smoothened (TF)
Patch
What is the receptor for Shh?
Patch
What happens to expression of smoothened (TF) after Shh binds Patch receptor?
Expression gets turned on (Patch receptor can no longer inhibit Smoothened expression)
What is the end result of Shh binding to Patch receptor?
Express Smoothened, which upregulates transcription of genes that specify ventral cell types
If you remove NC from neural tube, what happens to ventral cell identity?
There will be no ventral cells bc there is no Shh.
Shh is produced by NC and floorplate, which are not there (floorplate needs Shh production from NC to produce Shh itself)
What happens if you transplant a second NC into an early embryo?
A second neural plate will form, meaning that there will be 2 floorplates, meaning that 2 ventral identities will form
Which structure secretes BMP responsible for establishing dorsal identity?
Neural crest cells
BMP induces the expression of the TF ____, which is involved in regulating genes that form dorsal identity
Lmx1a
Interkinetic migration: During G1 phase, the soma is near the ___ surface
Ventricular
Interkinetic migration: During S phase, soma migrates toward the __ surface
Pial
Interkinetic migration: During G2 phase, which surface does the neuron migrate back to? Is it still connected to the other surface?
Ventricular
No, it is no longer attached to the pial surface
Cells at the ventricular surface can undergo 2 types mitosis to yield different daughter cells. What are the 2 types?
Symmetrical and asymmetrical
What types of neurons does symmetric mitosis result in?
Neural stem cells
What types of neurons does asymmetric mitosis result in?
- neuroblast
2. progenitor cell with limited mitotic potential
Defie pluripotent
Ability to differentiate into any type of cell
Are neural progenitor cells pluripotent?
No, they have limited differentiation properties - can only differentiate into neural cells, not ANY cell
What 2 types of cells do neural progenitor cells differentiate into?
Neuroblasts and glioblasts
Astrocyte development involves which 2 signals?
bHLH and Notch
Oligodendroycte development involves which 3 signals?
bHLH
Olig1/2
Nkx2.1
The gene products of which 2 signals are involved in neuron development?
Notch and bHLH
What is the correct order of differentiation:
a) oligodendrogenesis –> astrogliogenesis –> neurogenesis
b) astrogliogenesis –> neurogenesis –> oligodendrogenesis
c) neurogenesis –> oligodendrogenesis –> astrogliogenesis
c) neurogenesis –> oligodendrogenesis –> astrogliogenesis
T or F: neurogenesis still occurs in the adult brain
T, but in certain areas only
Which regions of the adult brain does neurogenesis still occur?
Dentate gyrus of hippocampus
Olfactory bulb
Cells in the olfactory bulb migrated from which structure?
Subventricular zone
What are iPS?
induced pluripotent stem cells - cells in which genetic info can be reprogrammed to mediate stem cell functions
How many genes are sufficient to induce a differentiated cell type to revert to a stem cell-like identity?
4
Neural crest cells undergo _____ transition
epithelial-mesenchymal
What is the end result of neural crest migration?
Formation of different types of ganglia
T or F: migration of neural crest cells in the embryo is limited
F - they can migrate all over the embryo
How do neural crest cells differentiate into different types of neural cells?
They are exposed to different concentrations of signals, and different signals
What is responsible for formation of different cell layers in the brain?
Interkinetic nuclear migration
Long distance neural migration occurs on ____.
existing axon tracks
Which 2 types of cells are long range migration especially important for?
cortical GABAergic interneurons
oligodendrocytes
Which brain structure is an excellent example of local neural migration?
cortex
T or F: cells furthest inside the cortex are the oldest cells
F - they are the oldest cells
How do you map migration of cells inside the cortical layer?
Label neurons with radioactive thimidine –> will observe that they migrate to different layers in the cortex
Cell migration from the ventricular zone to the pial surface is an example of what type of migration?
Local migration
Cell migration from ventricular to pial surface occurs along what?
Radial glia
Axon tracks is radial glia aren’t present
T or F: The only function of radial glia is to act as a scaffold for local neural migration
F - they can also differentiate into neurons
T or F: all neurons migrate along radial glia when they are present
F - these are called non-radially migrating glia
What are radially-migrating cells?
Neurons that migrate along radial glia
What is lissencephaly caused by?
Abnormal cell migration
What is the defining characteristic of lissencephaly?
Smooth brain - no folds that indicate different brain layers
T or F: children with lissencephaly appear normal at birth but show intellectual disability and seizures during their first year of life
T
What do mutations in the Reelin gene result in?
Abnormal layering of the cortex
Which transmembrane protein does Reelin bind to? What kind of kinase is activated? What is the end result?
ApoER
Soc kinase
Neuronal migration
T or F: one of the proposed functions of Reelin is that it stops neural migration at the right time
T - if Reelin is mutated, neurons will not stop migrating bc they don’t know where to stop
What is the optic chiasma in the frog?
The point at which the optic nerve from the right eye crosses to the left part of the brain, and the optic nerve from the left eye crosses to the right part of the brain
Where are growth cones located on the neuron?
At the tip of the axon
List 4 properties of growth cones
- highly dynamic
- enriched in cytoskeletal elements (actin and MT)
- composed of filopodia and lamellopodium
- enriched in cell surface receptors and signal transduction machinery
What do the cell surface receptors on growth cones do?
Detect chemoattractive/repellent cues at transitional points
Which cytoskeletal element are the filopodia enriched in?
Actin
Where is tubulin enriched at the growth cone?
Base of the growth cone - the most stable part
What drives actin elongation?
Monomers disassociating at one end of the actin molecule and associating at the other end
What is F actin?
The filamentous form of actin
What is G-actin?
The globular/monomeric form of actin
Where does F-actin assembly occur in the growth cone?
Leading edge of the filopodium
What initiates F-actin assembly at the filopodia?
- Filopodia has receptors that bind to attractive cues
- Receptor binding causes secondary messenger signalling (ex. Ca++) that drives actin polymerization
What drives actin or tubulin depolymerization in the filopodia/growth cone?
- Binding of repulsive cues to receptors on the filopodia
- initiates secondary messenger signalling that drives depolymerization
What drives filopodia movement?
Actin and tubulin polymerization and depolymerization. Polymerization promotes movement towards something, while depolymerization promotes movement away from something
What are the 2 distance scales that attractive/repulsive forces can occur on?
- long-distance attraction/repulsion
2. contact-dependent attraction/repulsion
Are cadherins Ca++-dependent?
Yes
Are all cell adhesion molecules Ca++ dependent?
No
Netrin signalling is attractive when it binds to what?
DCC homodimer
Netrin signalling is repulsive when it binds to what?
DCC-Unc5 heterodimer
Netrin signalling is attractive or repulsive based on what intracellular signal?
Levels of cAMP in the cell
Which structure is netrin secreted from?
Floorplate
T or F: dorsal commissural interneurons cross from ventral to dorsal side of due to Ephrin secretion from the floorplate
F - the interneurons cross from DORSAL to VENTRAL side due to NETRIN secretion from the floorplate
Dorsal commissural interneurons migrate towards which signal?
Netrin
Is netrin signalling contact-dependent attraction?
No - it’s long distance attraction
Notochord secretes repulsive signals to repel the ___
DRG
The Slit protein binds to which receptor?
Robo
What phenotype does robo loss of function result in?
Axons cross over randomly
What phenotype does Slit loss of function result in?
Axons can’t cross over
Are semaphorins attractive or repulsive? Work across long distances or contact-dependent?
Repulsive, contact-dependent
Which system are the Ephrins and Eph receptors involve in?
Retina-tectum mapping
