test 2 lecture 18 -19 nervous system Flashcards
The trilaminar embryo (aka trilaminar blastocyte) has three distinct layers
- ectoderm
- mesoderm
- endoderm
The central and peripheral nervous systems are entirely derived from the ___ layer.
ectoderm
The development of the central and peripheral nervous systems is initiated by the induction of the ___ (occurs during gastrulation).
neural plate
___ is the the process by which neural plate is generated from ectoderm
neural induction
__ directs neural induction
notochord (part of mesoderm)
ectoderm stays epidermal ectoderm by binding with ___
BMP4
ectoderm turns into neural crest by
Chordin, Noggin and Follistatin are secreted by the dorsal
mesoderm/notochord
They bind BMP4 molecules inhibiting BMP4 interaction
act as BMP antagonists
antagonists to the protein and NOT the receptor
___ of BMP4 signaling in the ectoderm is required to convert the ectoderm into neural tissue (mediated by the dorsal mesoderm)
Inhibition
Noggin, Chordin and Follistatin act as ___
BMP antagonists
bind to BMP protein and prevent BMP from binding to its receptors
___ are secreted by the dorsal
mesoderm/notochord to stop BMP
Chordin, Noggin and Follistatin
___ is the default state of the ectoderm
(in the absence of BMP4 signaling)
Neural fate
transformation of the neural plate into the neural tube
Neurulation
The nervous tissue induced by BMP4 inhibition is anterior in character (___).
forebrain
neural induction is ___ neurulation
NOT
Neurulation = transformation of the neural plate into the neural tube
Neural Induction= The process by which the dorsal mesoderm induces the overlaying ectoderm to form neural tissue
The central nervous system is regionalized along the ___ axis.
anterior-posterior (AP)
what are the two models of induction and AP patterning of the neural plate
which one is correct?
different inducers at different spots
or
gradient of inducer
gradient is correct
Induction and AP patterning of the neural plate is a two-step process
Activation: Induction of anterior neural tissue mediated by inhibition of BMP4 signaling in the ectoderm by Noggin, Chordin, and Follistatin (made by notochord)
Transformation: A distinct set of signal(s) posteriorize the neural tissue. (FGF, retinoic acid, Wnt-3a_
What are the three posterior neural inducers
fibroblast growth factor (FGF) family,
Retinoic acid
Wnt-3a
neurulation
neural plate transforming into neural tube
two neural tube defects
errors when neural plate fails to close properly into neural tube
anencephaly- absence of major portion of brain/ skull
spina bifida- spine/spinal cord defect
The prospective brain is initially subdivided into three primary vesicles:
Forebrain (prosencephalon)
Midbrain (mesencephalon)
Hindbrain (rhombencephalon)
• Forebrain (prosencephalon) becomes
Midbrain (mesencephalon) becomes
hindbrain becomes ___
___ is the boundary between the midbrain and the hindbrain):
Isthmus
Isthmus
•the boundary between the midbrain and the hindbrain)
a critical region for the formation and the patterning of the midbrain.
•express signaling molecules (Wnt-1 and FGF8); acts as an organizing center.
if Wnt 1 is inhibited what will happen to midbrain?
if FGF8 is placed somewhere else what will happen?
will not develop
2nd midbrain will develop but in wrong direction
•The hindbrain is divided into periodic swellings known as ___
rhombomeres.
•The ___ represent separate “territories”, such that cells from one rhombomere cannot mix with cells from adjacent rhombomeres.
rhombomeres
In the hindbrain, ___ encode positional values along the anterior-posterior axis of the nervous system.
Hox genes
The identity of each ___is defined by the expression pattern (specific combination) of Hox genes.
rhombomere
It is unclear how Hox genes become activated at appropriate levels, although ___, ___, and ___ are likely regulators.
Retinoic Acid (RA)
Egr2
Mafb
how does retinoic acid effect hindbrain
more RA in posterior, effects which hox gene is expressed and which rhombomere is made.
if experiment is done and more RA is added to anterior of hindbrain then rhombomere 4 will form instead of rhombomere 1,2,3
zones of neural tube
marginal zone: neuroblasts, glioblasts
Ventricular zone: neural stem cells
Neuroepithelial cells are the precursor cells for ALL of the cells in the CNS (with one exception). what is the exception?
microglial cells
immune cells of the CNS
these come from mesenchymal cells
neuroepithelium can turn into what two major types
glial lineage progenitor cells
neuronal lineage progenitor cells
glial lineage progenitor cells can turn into
ependymal cells- lining of ventricles
type 1 astrocyte
Type 2 astrocyte
oligodenrocytes
Astrocytes
come from gilial lineage progenitor cells
Supporting cells: give physical and metabolic support, can regulate neuronal activity
Oligodendrocytes
schwann cells
Myelinating cells: wrap axons with myelin, increasing speed of electrical transmission
neuronal lineage progenitor cells lead to
mature neuron
1,000-10,000 types; electrical activity executes all the functions of the nervous system
what can help orient ventral vs dorsal neural tube
group of non neural cells
roof plate
floor plate
notochord will cause what to form in the neural tube?
floor plate
motor neurons
The Notochord is the source of two inductive signals.
local signal that induces floor plate differentiation at the midline
long-range signal that induce motor neurons on each side
The ___, once induced, acquires the ability to generate both short- and long-range signals.
floor plate
Notochord secretes ___ to induce the formation of floor plate in the neural tube
sonic hedgehog Shh
After formation of the Floor plate of the neural tube, the floor plate will secrete ___ making a gradient
Shh (sonic hedgehog)
___ acts as a morphogen to generate neuronal diversity
Shh
Graded amounts of Shh generate distinct populations of motor neurons and interneurons in the ___ portion of the spinal cord.
ventral
dorsal differentiation of neural tube is by
Transforming growth factor (TGF-b) family
Bone morphogenetic proteins (BMPs)
Overlapping expression in the dorsal spinal cord
Neuronal diversity in the dorsal spinal cord is established as a result of a diversity in signal identity rather than signal intensity.
Neuronal diversity in the dorsal spinal cord is established as a result of a ___ identity rather than signal intensity.
diversity in signal
loss of GDF7, a BMP related factor led to the selective loss of a single class of dorsal interneurons
diversity and pattern in the neural tube
dorsal by different signals
ventral by gradient of Shh
During neurulation, the neural crest is at the most ___ region of the neural tube
dorsal
•To migrate, neural crest cells will undergo ___
epithelial-to-mesenchymal transition (EMT)
a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain ability to migrate (and invasive properties).
what are some things neural crest cells can turn into
Upon neural tube closure, neural crest cells delaminate in a ___and migrate along specific routes.
rostro-caudal wave
cranial neural crest cells turn into
derived from the hindbrain (rhombomeres 4,5,6)
migrate dorsolaterally
cells enter the pharyngeal pouches (2 and 3) and arches where they contribute to the thymus, bones of the middle ear and jaw, and the odontoblasts of the tooth primordia.
cartilage, bone, cranial ganglia and connective tissue of the face
cardiac neural crest cells turn into
septum of the outflow tract of the heart (separates the truncus arteriosus into the pulmonary artery and aorta) and wall of large arteries
neural crest induction
notochord releases anti BMP (noggin, chordin, follistatin) neural crest has happy medium of anti BMP
paraxial mesoderm release Wnt and FGF
non neural ectoderm release Wnt
Neural crest release Notch/Delta which inhibit BMP
The __cells are a stem cell-like population. Some of these cells are multipotent which means __
neural crest
are able to generate numerous cell types (bone, cartilage, smooth muscle, neurons, pigment cells)
neural crest diversification is dependent on local factors, an example is glial growth factor stimulates differentiation into ___, while endothelin-3 stimulates differentiation into ___
autonomic neurons
melanocytes and enteric neurons formation.
All sensory cells of the peripheral nervous system (PNS) develop from various sources, but primarily from ___ and from thickenings of the ectoderm in the head region known as ___
neural crest cells
ectodermal placodes.
The cell bodies of these sensory cells are located ___ the central nervous system.
outside
The __consists of cranial, spinal and visceral nerves and ganglia.
PNS
The spinal ganglia (dorsal root ganglia) are exclusively derived from ___ that migrate and accumulate on each side of the spinal cord to form the sensory spinal ganglia.
neural crest cells
Spinal ganglia cell bodies project branches towards the ___part of the spinal cord through the ___ root of the spinal nerves.
dorsal
dorsal
neural crest contributes to what part of the PNS
sensory neurons
autonomic neurons
enteric neurons
The sensory components of the ___ originate from cells derived from the neural crest and the ectodermal placodes that aggregate outside the brain.
cranial nerves
The sensory components of the cranial nerves
these collections of nerve cells bodies are called ___. These are functionally similar to the spinal (dorsal root) ganglia in the trunk.
sensory cranial ganglia
In general, ___ of the cranial nerves send out two branches, one that enters the brain and one that is connected to a specific peripheral sensory organ
sensory ganglia
MY= Myelencephalon
MT= Metencephalon
MS= Mesencephalon
OV= otic vesicle
ED= endolymphatic duct
defects in the formation of NC and its derivatives
Neurocristopathies
3 neurocristopathies
Result of defects in neural crest cells themselves but also of defects in the environment through which they migrate.
Defects affect only a single derivative of the neural crest, whereas other defects result in a wide array of seemingly unrelated clinical manifestations.
Frontonasal dysplasia= (craniofacial deformities)
DiGeorge syndrome= (craniofacial and conotruncal heart defects).
Waardenburg-Shah syndrome (and Hirschrung’s disease)= (hypopigmentation and aganglionic megacolon) Endothelin B receptor mutations (mice)
- Lethal white syndrome (horses)*
- Hypopigmentation and deafness (Dalmations)*
DiGeorge Syndrome
Rare congenital disease (1:4,000 live birth).
caused by large deletion in chromosome 22- Tbx1 not formed correctly
Symptoms :
- congenital heart defects; VSD (ventricular septal defect)- cardiac neural crest cell
- craniofacial facial malformation (cleft palate)- cranial neural crest cell
Waardenburg-Shah syndrome
pigmentation defects (white streak in hair) and deafness. (trunk neural crest cell issue)
Hirschsprung’s disease: absence of enteric neurons in the distal portion of the colon (aganglionic megacolon), congenital megacolon is occurring in approximately 1:5000 live births; (issue with sacral neural crest cells)
Hirschsprung’s disease:
absence of enteric neurons in the distal portion of the colon (aganglionic megacolon), congenital megacolon is occurring in approximately 1:5000 live births; (issue with sacral neural crest cells)
issue with endothelin B receptor gene
“balloon man”
Lethal white syndrome
•Affected foals are born after the full 11-month gestation and externally appear normal (but with DISTINCT coloration – all white coats, blue eyes
Have a nonfunctioning colon, develop colic and die within days
Mutation in the endothelin-B receptor gene causes lethal white syndrome when homozygous
Horses heterozygous for the mutation may exhibit a white-spotting pattern called “frame”.
Hypopigmentation and deafness in Dalmatians
•There is a strong association between pigmentation defect and deafness in Dalmatians.
Defective cell type is the neural crest-derived melanocytes
•Melanocytes are present in normal hearing tissue (intermediate cells), but absent or reduced when deafness occurs.
Melanocytes help control the endocochlear potential which is required for normal hearing.
adult neural crest stem cells
self-renew and can give rise to thousands of neurons, glia and smooth muscle cells
been identified in the peripheral nervous system of adult animals.
•Identified in rat sciatic nerve and gut.
___ and ___ have an early role in specifying the identity of cell types along the dorsoventral axis of the spinal cord, but as development proceeds, more specialized cell types are generated.
Shh and BMP proteins
___ in the developing spinal cord can be subdivided on the basis of the position at which their cell bodies are located, and by their axonal projection pattern.
Motor neurons
Median motor column is found
along the entire spinal cord
project their axons to axial muscles
Lateral MC medial
project their axons to ventral limb muscle
Lateral MC lateral
project their axons to dorsal limb muscle
(lateral-lateral motor column)
column of Terni
project their axons ventrally (sympathetic neurons)
Subclasses of motor neurons are organized into longitudinal columns that occupy distinct, and in some cases, discontinuous domains along the ___ axis of the spinal cord.
rostrocaudal
•Columnar subclasses of motor neurons can be distinguished by the combinatorial expression of the ___of transcription factors.
LIM family
What class of molecules control the expression of molecules involved in the guidance of motor axons along different pathways to their specific targets in the periphery?
LIM family
Within each motor column, motor neurons are further subdivided into ___, each innervating a specific muscle in the limb.
pools
How are the subtype identities of motor neurons established?
we don’t know
maybe signal from the notochord?
A functional ___ depends not only on the differentiation and positioning of specialized neural cells, but also on the specific connections these cells make among themselves and their peripheral targets.
nervous system
•___ at the tip of the extending axon is the major force in guiding it to its destination.
Growth cone
•In general, the growth cone moves in the direction where its ___makes the most stable contact.
filopodia
•Filopodia (microspikes) - slender cytoplasmic projections; extend beyond the leading edge of lamellipodia in migrating cells. They contain actin filaments cross-linked into bundles.
___: slender cytoplasmic projections; extend beyond the leading edge of lamellipodia in migrating cells. They contain actin filaments cross-linked into bundles.
Filopodia (microspikes)
4 guidance mechanisms for axons
long range:
chemoattraction (netrins)
chemorepulsion (samaphorins)
short range
contact attraction (cadherins)
contact repulsive (ephrins)
