L2: Early Development of CNS Flashcards
Gastrulation starts at day 7. It is important b/c
- forms ectoderm, endoderm, mesodern
- forms midline/primitive streak and notochord
- neural induction (ectoderm knows to become neural ectoderm)
1st thing in neurogenesis is
formation of midline/primitive streak
At 18 days, neurulation begins by forming the neural plate. The neural plate is formed by?
The neural plate is above the notochord and is formed by neural ectoderm.
What kind of effect do bone morphogenic proteins (BMPs) have on neurulation?
BMPs work on the level of transcription to stimulate ectoderm to become epidermis; and NOT neural ectoderm.
What does notochord secrete to help with neural induction?
Notochord secretes Chordin and Noggin which will inhibit BMPs and promote ectoderm to become neural ectoderm (neural induction).
“default state” of cell
Default state for cell is to become a neuron
At 18 days, neural plate forms, then it will invaginate to form a neural groove, then a neural tube. As neural tube forms, neural crest cells pinch off. What are neural crest cells?
they can become give rise to lots of different cells
- cranial neural crest
- trunk neural crest
- vagal and sacral neural crest
- cardiac neural crest
the neural tube has a floor plate and roof plate that act as signaling functions. What is highly expressed in notochord & floor plate?
sonic hedgehodge responsible for dorsal-ventral patterning, leading to ventral cell fates
Spina bifida
failure of neural tube to close due to folic acid deficiency
Ancephaly
no formation of anterior portion of brain due to failure of neural tube to close
Holoproencephaly
failure of frontal brain lobes to split at midline due to problems with dorsal ventral patterning
Shh pathway can lead to what clinical issues?
1) holoprosencephaly
2) cancers; shh plays a role in cell proliferation
3) cyclopia
Cyclopamine
Shh antagonist leading to cyclopia
What is highly expressed in the roof plate?
BMPs which will lead to dorsal cell fates
Retinoic acid (RA) and fibroblast growth factor (FGF) play a huge signaling role in which pattern pathway?
dorsal-ventral patterning
Anterior-posterior patterning overlaps with neural induction. What does A-P patterning result in?
definining the spinal cord, rhombencephelon (hindbrain = pons, medulla, cerebellum), midbrain, proencephelon (forebrain)
Which genes play a huge role in A-P patterning?
HOX genes/homeotic genes (particularly impt in hindbrain & spinal cord formation); OTX genes
Steps of neural system expansion
- involve both asymmetric & symmetric proliferation
1. symmetric division makes more neural stem cells (increasing size of of ventricular zone, and size of brain)
2. early asymmetric division makes 1 neural stem cell, 1 neural precursor
3. symmetric divisions will eventually lead to 2 neural precursors and less and less pluripotent neural stem cells
Where do neurons proliferate and differentiate?
ventricular zones
most of gliogeneis occurs after neurogenesis. What are some mechanisms that guide gliogenesis?
astrogliogenesis
- NOTCH will stimulate stem cells to astrocyte precursors
- proneural bHLH will inhibit stem cells to become astrocytes
oligodendrogenesis
- Olig1/2 will stimulate stem cells to become oligodendrocytes
- proneural bHLH will inhibit
What is the effect of NOTCH on neurogenesis?
NOTCH signaling will inhibit proneural bHLH, keeping neural stem cells as neural stem cells. Therefore, NOTCH is inhibitory to forming neurons.
In presence of another cell’s release of low/mod levels of NOTCH, NOTCH can activate thru delta bHLH genes. What then will happen?
bHLH genes will stimulate neural stem cells to become neural precursors, and then to neurons.
When does neurogenesis finish?
middle of 2nd trimester
T/F: Defects during 1st 3 weeks are not deadly.
False; it will be deadly b/c neurogenesis normally finishes in middle of 2nd trimester
Radial migration
radial migration is how cortex is formed from an inside out manner in which 1st born cells migrate from ventricular zones to pial surface and subsequent cells take same radial migration & migrate above the previous born cells.
Reelin mutation
reelin is an ECM protein that helps with radial migration. hence, reelin mutation will lead to lissencephaly(smooth brain)
Are interneurons made in the ventricular zones like other neurons?
No, interneruons are made in medial & lateral ganglionic eminences
Do interneurons also display radial migration?
No, they migrate tangentially.
