Nervous system development Flashcards
Notochord
major axial signaling center of the trunk: does not stimulation formation of anterior parts of the brain or head
head region is organized by prechordal plate
What is the “head region” organizer?
the prechordal plate
What DOESNT the notochord stimulate formaiton of?
the anterior parts of the brain/head structure
Primitive streak is replaced by the
notochord:
how is the primitive streak replaced
migrating ectoderm cells from “median column”
cells move posterior to prechordal plate and become notochord
also called chordamesoderm
The notochord stops growing just
inferiorly to the buccopharyngeal membrane
Notochord is the primary inducer in what
early embryos
indcues overlying ectoderm to form neural plate —> neutral tube
What does the notochord induce
overlying ectoderm (neural plate) to form neural tube
What becomes of the notochord?
it will form part of intervertebral discs (nucleus pulpous)
Induction of nervous system: 2 phases
Primary and Secondary neurulation
Primary neurulation (time)
wks 3-4
Secondary neurulation (time)
wks 5-6
how does nervous induction occur in terms of signaling molecules?
probably secrete inhibitory signals that obstruct other inhibitory signals, allowing the overlying ectoderm to differentiate into neural tissue as a default state
Blue box quote on neurulation: summarize in own words
signaling molecules from notochord dont act directly on ectoderm but inhibit other factors like BMP-4.
inhibition of BMP-4 = what during neurulation
neural formation
Molecular regulation of neural induction
what molecules inhibit other molecules in terms of notochord signaling
Noggin, Chordin inhibit BMP-4 in overlying ectoderm
Wnt3a/FGF inhibit BMP-4 in overlying ectoderm
What happens if BMP-4 isn’t blocked during neurulation?
the overlying ectoderm becomes SKIN instead of neural plate
Cellular adhesion molecules involved in neural induction
CAMs. they keep cell clusters together
two big ones are E and N cadherin
they only bind to like cadherins
E cadherin
epidermis formation
N cadherion
neural plate formation
What are the 4 stages of neural tube induction?
1) neural plate induction
2) neural fold and neural groove induction
3) contractile fibers in neuralepithelia pull folds together
4) fusion of neural plate to form neural tube
what signaling molecule permeates the epidermis?
BMP4
what does BMP4 induce after neural tube formation?
induces a new signaling center in the roof plate, which also secretes BMP-4
Roof plate and Floor plate of neural tube
overlying epiderm secretes BMP4 which induces roof plate to become a signaling center (also secreting BMP4)
underlying notochord signals floor plate with Shh to become a signaling center, which will also secrete Shh
neural tube concentration gradient
dorsally = double BMP-4 gradient from epiderm and roof plate
ventrally = Shh gradient from floor plate
what does the Shh/BMP-4 concentration gradient do
it specifies the identity of the neurons in the tube by reading the concentration of the two factors
creates an AP-Dorsal/Ventral coordinate system along which cells can be parceled into unique fates
along the longitudinal axis: specifies Hox gene expression
Rachischisis
neural tube defects
what happens when neuropores dont close
the cranial neuropore fails to develop, undeveloped brains are exposed
anencephaly
neuropores fail to close, unviable life form
Waves of neural tube closure
at least 5 waves of closure in normal embryogenesis
anencephaly is failure of wave
2 of neural tube closure
Spina bifida is wave
1 and 5 of neural tube non-closure
what kind of cranial structure would we see in spina bifida versus ancencephaly?
normal spina bifida, caudal agenesis
shrunken in anencephaly
Encephalocele
failure of wave junctions at 4/1
cranial defect with herniation of intracranial content, most common in occipital region
cariants can contain meninges, brain, and ventricular system
produces a meningoencephalocele
Spina bifida occulta
vertebral column doesnt close, typified by a tuft of hair
Spina bifida with meningomyelocele
large, skin covered bulge at posterior/lower lumbar spine.
cavity is lined by meninges and spinal nerves herniate into cavity
Meningomyelocele versus Meningocele
Meningomyelocele is a myelocele with meninges
Prenatal surgery for spina bifida
most of the damage occurs late in pregnancy
spina bifida sac allows amniotic fluid in to the hold of the spin, damaging developing spinal cord = life long paralysis
secondary neurulation
caudal to posterior neuropore: remaining neural tube is formed by secondary neurulation
associated malformations of secondary neurulation
myeldysplasias
coccgyeal pits
large superficial capillaries
Tethered Cord Syndrome
conus medullaris and filum terminale are abnormally attached to the defective vertebral column
constant traction damages the spinal cord
can lead to subsequent loss of sensation from the lower limbs and problems with bladder control
How does folic acid prevent neural tube defects?
.4 mg of folic acid decreases NT defects by 70%, mode of action poorly understood
believed to be a homocysteine to methionine transformation
NTDs: metabolic or dietary?
maybe both
NTDs: what test will be elevated if present?
alpha fetoprotein AFP testing
AFP
alpha fetal protein
produced in the liver. in fetus with open NTD, AFP leaks across the defect into the amniotic fluid across placenta and into maternal serum
AFP elevatation can be tested in
can be tested in maternal blood
AFP is produced in the
fetal liver
Derivatives of neural ectoderm
which develops from the neural tube and which develops from neural crest?
sensory ganglia and PNS eyes teeth skin CNS PINEAL body posterior pit.
all CNS by neural tube, all PNS by neural crest
Albinism
autosomal recessive, global reduction or absence of pigment in skin, hair eyes
Vitiligo
loss of melanocytes
autoimmune disorder
can be reversed
ED syndrome
ectoderm dysplasia syndrom
EDS
sparse hair, malformed teeth. requires at least TWO identifications (so teeth and hair would be two in this case)
effects both men and women
Epithelial ectoderm —>
oil
Lateral mesoderm —>
appendicular skeleton
endoderm —>
lining of urogenital track, vascular system, guts, liver, pancreas etc