Lecture 2: Early Development of the Nervous System Flashcards
During gastrulation, the midline is also called the _______. It is defined by formation of the ______, and is critical for formation of all tissue, including the _______.
primitive streak
notochord
CNS
Gastrulation begins with invagination in the _____, leading to formation of three different ______ (____, ____, ____)
blastula tissue layers (ectoderm, mesoderm, endoderm)
Early neurulation is coincident with ________ signaling events, and induces the _______.
gastrulation
neural ectoderm
What is the very first event in neurulation?
notochord formation
Notochord formation is central to gastrulation by defining the ______ of the embryo and inducing formation of the ______.
midline
neural ectoderm
What are neural ectodermal cells precursors of?
neural cells
What is the default fate in neural induction?
neural fate
What does blocking BMP cause?
cells adopt neural fate
What are factors which inhibit BMP? Where are they produced?
Chordin, noggin, follistatin
notochord
What does BMP activity drive formation of?
epidermis
BMPs bind _____ and a ____ complex, which is transported to the nucleus to mediate transcription
receptor tyrosine kinases
SMAD
What are BMPs, FGF (retinoic acid), insulin GF, and inhibition of Wnt signaling involved in?
neural induction
What are cells which make up the neural tube?
Neural stem cells
After neural induction, the formation of _____ happens very rapidly. How is this formed?
- neural tube
- lateral margins of the neural plate fold inward
From what direction does the neural plate close to form the neural tube?
Both directions - anterior and posterior
What two compounds are important for neural tube formation?
Folic acid
B-complex vitamins
As the neural tube closes, the _____ pinches off
neural crest
What 4 structures does the neural crest give rise to?
- Cranial neural crest
- Trunk neural crest
- Vagal and Sacral neural crest
- Cardiac neural crest
What components come from the cranial neural crest?
- Cranial ganglia
- Bones and cartilage in face and head
What components come from the trunk neural crest?
- DRGs
- sympathetic ganglia
- adrenal medulla
- melanocytes
What components come from the vagal and sacral neural crest?
parasympathetic ganglia
What components come from the cardiac neural crest?
- cartilage
- melanocytes, neurons of pharyngeal arches
- regions of the heart
What neural tube defect results from failure of the posterior end of the neural tube to close?
Spina Bifida
What neural tube defects result from failure of the anterior end of the neural tube to close?
ancencephaly, holoprocencephaly
What is the signal for ventral patterning?
Sonic Hedgehog
What is the signal for dorsal patterning?
TGF-beta family (BMPs)
On what signaling molecule is formation of the neural plate and neural groove dependent?
Sonic Hedgehog
The neural crest gives rise to cells in the _____ nervous system.
Peripheral
What is the effect of Shh signaling absence in brain development?
holoprocencephaly - telecephalon fails to bifurcate
With what event does anterior-posterior patterning overlap?
neural induction (gastrulation)
What 4 features does anterior-posterior patterning give rise to?
- Spinal chord
- Rhombencephalon
- Mesencephalon
- Prosencephalon
What are the two feature of the rhombencephalon? What does each give rise to?
Metencephalon –> pons
Myelencephalon –> medulla
What does the Mesencephalon, which results from A/P patterning, give rise to?
midbrain
What are two features of the prosencephalon? What does each give rise to?
Diencephalon –> thalmus, retina
Telencephalon –> forebrain
What are Hox genes involved in?
anterior/posterior patterning in posterior CNS
What do OTX2 knockout embryos lose?
anterior neural structures
Neural stem cells and neural progenitor cells divide and differentiate in the _____ zone to give rise to all cells in the ______.
ventricular
CNS
Describe the divisions which occur in early, middle, and late development during generation of the nervous system.
- Early: Neural Stem Cells –> symmetric division –> 2 Neural Stem Cells
- Middle: Neural Stem Cells –> asymmetric divison –> 1 Neural Stem Cell, 1 Neural Progenitor
- Late: Neural Stem Cells –> symmetric divison –> 2 Neural Progenitors = NSCs disappear
What do neural progenitors give rise to?
neurons and glia
_____ and ______ control neural progenitor differentiation.
Notch
proneural basic-helix-loop-helix transcription factors
Notch signaling through _____ requires ______.
Delta
Cell-cell contact
What happens at low/moderate levels of Notch stimulation through Delta?
bHLH genes are activated –> high expression of bHLH genes –> cell differentiation into neuron
How does Notch become hyper-activated? What happens next?
- bHLH activation upregulates Delta –> hyper-activation of Notch
- -proneuronal bHLH genes are shut off, kept in pluripotent neural stem cell state
Gliogenesis starts AFTER the peak of _____
neurogenesis
Astrogliogenesis reuses signaling pathways. Astrogliogenesis differentiation from neural progenitors is _____ dependent and is inhibited by ____ genes.
Notch
basic-helix-loop-helix
Are oligodendrocyte generation and astrogliogenesis induced by the same or different factors?
Different
- Astro - Notch
- Oligo - Oligs, Nkx 2.1
After neurogenesis, astrogliogenesis and oligodendrogenesis occur. Which happens first?
Neurogenesis –> Oligo –> Astro
By when are neurons in most brain areas generated?
middle of 2nd trimester
When does the majority of gliogenesis occur in humans?
after birth
When does almost all of myelination occur in humans?
After birth, until age 20
What effect can cocaine, marijuana, and alcohol use during pregnancy have on the developing brain?
Decrease in size of grey matter cells in cortex and caudate
By what point in pregnancy is primary neurulation complete?
first 3 weeks
In what manner does the cortex form? What is this pattern due to?
inside-to-outside
radial migration
In radial migration, the 1._____ neurons migrate radially along 2._____ to the 3._____, and each subsequent generation of neurons migrates 4._____ the earlier born neurons.
- radial
- radial glia
- cortical plate
- past
What is the dual nature of radial glia?
- give rise to neurons
2. provide a scaffolding on which these neurons can migrate to appropriate destination
Mutation in the ECM protein, reelin, disrupts the process of cortical formation. What is the result?
cortex is inside-out
Interneurons are derived from the _____ and _____ ganglionic eminences, and cannot migrate radially. Instead, they migrate _____. This process involves which 3 txn factors?
- medial and lateral
- tangentially
- DLX1, DLX2, Mash1
