Lecture 10 Flashcards
Early development dates
Fertilization
Embryo
Days 3-4: Morula dividing
(2^4 = 16 cells)
Days 5-9: Blastocyst
(2^7=128 cells)
Embryonic stem cells
- ectoderm (brain+skin)
- mesoderm (muscle blood bone cartilage)
- endoderm (lung gut liver)
- germline (sperm egg)
Neurulation
Part 2
Day 18: Neural plate
most dorsal
ecto + primitive streak
meso + notocord
endo
most ventral
Day 20: Neural groove
neural crest begins to fold from ectoderm and form the neural tube
Day 22: Neural tubs formed
mesoderm becomes somite (will become skeleton and skeletal muscles)
Day 24:
beginnings of the…
- CNS (neural tube)
- PNS (neural crest)
- Skeleton and axial muscles (somites)
= tube zips up
Neurogenesis
Part 3
neural stem cells
- divide symmetrically to produce two stem cells
- transition into radial glial cells
Radial glial cells
- divide asymmetrically to produce a neuroblast + another radial glial cell (neuroblasts climb up these)
Neuroblasts
- neuron precursors
- become neurons
= no further cell division - migrate along radial glia to their destinations
Cell migration
from neural tube lumen (ventricle) out towards pial surface (membrane that covers outer brain surface)
Cortical layers
develop inside-out
layer 6 closest to ventricle
- oldest neurons
layer 2 closest to pial surface
- newest neurons
layer 1 = no cell bodies, develops first
Spina Bifida
+ risk factor
the neural tube fails to fully close caudally
two forms: open or oculta (milder, nerves don’t protrude through the skin)
Risk factor: insufficient folate/vit B9
- needed for DNA/RNA production during mitosis
exposed nerves may result in infection, affect bladder and bowel function, and cause paralysis
Anencephaly
the neural tube fails to fully close rostrally
much of brain does not form
also due to insufficient folate/vit B9
Lissencephaly
cell migration does not occur properly
= smooth brain
- DCX is a protein that normally stabilizes microtubules during cell migration
- gene for this on X chromo
Males
- affects migration of all neurons = only 4 partially formed layers
Females
- affects only some neurons
= stop migrating early
- gives appearance of two cortex layers only
symptoms
- difficulty eating and swallowing
- seizures
- intellectual impairment
How do axons know where to grow + how do they do it + speed
Growth cones!
microtubules create lamellipodium out of tubulin-binding subunits that polymerize
create filopodium “fingers” that move towards the attractive cue using actin from g to f actin
away from the main lamellipodium “palm”
advance 1mm/day
similar speed to slow axonal transport
regulated by intracellular calcium concentration
3 axon guidance factors
- Tropic molecules
chemoattraction
- attract growing axons to source
- ex. netrins - Repelling molecules
chemorepulsion
- ex. slit, semaphorins - Non-diffusible molecules
contact attraction or repulsion
ex. ephrins, Cadherins
Decussation in the optic tract
In relation to chemoattractants
Ephrin (contact repellent) produced
Nasal retinal axons
- no ephrin receptors
Temporal retinal axons
- have ephrin receptors
= repelled by the ephrin present in chiasm glial cells
Decussation in the spinothalamic tract
Chemoattractants
Slit is a chemorepellent and ligand that repels Robo1 and Robo2 receptors on growth cones
Netrin is a chemoattractant
Both are produced by floor plate (midline) cells
axons that express less robo receptors bind to slit less = not very sensitive to being repelled
instead attracted by netrin
then put on more robo receptors so they don’t decussate again
Robo3 receptor
different bc it doesn’t bind to slit
in mammals
dn’t know what its ligand is
attracted to midline
once decussated, reduces its expression of Robo3 (opposite of 1/2)
Rat whiskers and Robo3
no Robo-3 = contralateral decussation (normal) AND ipsilateral (not normal)
Rat auditory system and Robo3
no Robo3 = no decussation
from cochlear nucleus to contralateral MNTB
Rat VOR system and Robo3
2 decussations normally
one is from abducens to principal ocular nerve
no Robo3 = doesn’t have this decussation
Human loss of Robo3 issue
no Robo3 can cause LCST to not decussate
= move left activates left side of brain
Trophic factors
- produced by target tissue
- bind to receptors on the growth cone
- nurture axons at their destination
- support presynaptic neurons and promote dendritic and axonal elaboration once the target is reached
ex.
- nerve growth factor (NGF) to free nerve endings
- neurotrophins (NTs)
NT-3 to muscle spindle
NT-4/5 to hair follicle - brain-derived neurotrophic factor (BDNF) to merkel cells
Rita Levi-Montalcini + Stanley Cohen
- Discovered Nerve Growth Factor (NGF)
- Purified NGF from mouse tumors
- Showed NGFs effect on chick embryonic neurons
Trophic competition
trophic molecules in limited supply from the target tissue
= presynaptic axons compete for space and survival
one axon on each muscle fiber wins
Hebb’s postulate
LTPs with synapses strengthened over time can undergo a conformational change to increase both of their efficiencies
long-term LTP maintenance
Carla Shatz
- Based on Hebb’s postulate
“Neurons that fire together, wire together” “out of sync, lose your link”
Monocular deprivation
- ocular dominance column development is activity-dependent
- if deprived during critical period, non-deprived eye will heve a much larger space dedicated (larger stripes)
competition
permanent loss even when opened again
Ambylopia
impaired vision that is not caused by problems with the eye itself
ex. monocular deprivation causes less branching
causes amblyopia
Critical period for cats
0-2.5 months
respond ONLY to the never sutured eye
later suturing
= no impact
Calcium imaging
Fluorescent protein injected into a cell
Excited by a certain wavelength of light photon = gains energy
Then decays back to lower energy level
= gives light and heat of a different, higher wavelength (stokes shift)
Fura-2 indicates calcium
Excited at UV, emission at green
Normally emits the same amount of green for 340/380 nm UV light
With calcium present: emits more green light for 340 nm UV than 380 nm UV
Less green = more calcium (proportional)
In-vivo or in-vitro
Can put indicators in through many different methods (whole-cell patch clamp, through viruses, transgenic mice, etc. )
