Early Development of NS Lec 2 Flashcards
Gastrulation
Day 18 Ectoderm, Mesoderm, endoderm defines -midline -anterior/posterior -dorsal/ventral
Neural induction
BMPs- push ectoderm towards epidermal state
Inhibitors of BMP
Produced by notochord
- Chordin
- Noggin
- Fillistatin
Blocking BMP
Default
induces cells to take on neural fate
BMP signaling
BMP binds serine kinases and SMAD complex
SMAD to nucleus- mediates transcription
SHH dependent
FMF signaling
Critical for neural induction prior to BMP inhibition
Neurulation
Day 18-24
Neural tube formed after induction
Stem cells make up tube
Whats important for neural tube closer
Folic acid and B-Complex vits
Cranial Neural crest
Cranial ganglia
bones
Cartilage in face and head
Trunk neural crest
DRG
sympathetic ganglia
adrenal medulla
melanocytes
Vagal and sacral neural crest
parasympathetic ganglia
Cardiac neural crest
cartilage
melanocytes
neurons of the pharyngeal arches
regions of the heart
Ventral signal
motor
Floor plate
SHH
Dorsal signal
sensory
roof plate
mainly BMP
SHH signaling
SHH PTC SMO GLi Transcription -ventral (motor neuron) fate
Developmental defects without SHH
Holoprosencephaly
Cyclopia
Anterior/posterior patterning
overlaps neural induction, which overlaps gastrulation
- spinal cord
- Rhombencephalon
- Mesencephalon
- Proencephalon
Rhombencephalon
Methencephalon-pons
myelencephalon-medulla
mesencephalon
midbrain
proencephalon
diencephalon- thalamus and retina
telencephalon- forebrain
HOX genes
Posterior CNS involved in differences in -spinal cord -medulla -pons NO brain HOX
Ventricular zone
cells surround CSF
NSC and neural progenitor cells divide and differentiate here
Neural stem cells
Unlimited renewal
give rise to all cells in CNS
Progenitor cells
Derived from neural stem cells
Neurons OR glia
Not unlimited renewal
Neurogenesis time line
Neurons- by 2nd trimester
Gliogenesis- after birth until 20yo
almost no myelination at birth
Early development
NSCs divide symmetrically
-increase size of ventricular zone and brain
Later development
NSCs divide asymmetrically
-1 NSC and 1 Progenitor
Late development
NSCs divide symmetrically
-give rise to 2 progenitor
Regulating neural cell differentiation
Notch and bHLH
Requires cell to cell contact
Notch
Through delta- intracellular notch cleaved goes to nucleus activates bHLH genes positive feedback loop -bHLH upregs delta bHLH primed to differentiate into neuron
Notch hyperactivated
in surrounding cells to shut off bHLH and keeps cells pluripotent
Radial migration
Inside out manner
Cells closest to VZ form first
Radial glia
extends from VZ to pail surface
- neuroblast migrate along until they reach pail
- give rise to neurons and provide scaffolding
Primary neurulation
Complete with first 3 weeks
-after which neural precursor and neural development begins
brain extremely sensitive to nutrition and environmental toxins
Smaller brain
decreased amount of gray matter in cortex and caudate