Development of the Central Nervous System Flashcards
1
Q
Neural Plate
A
Surface Ectoderm that gives rise to the CNS
2
Q
Neural Tube Formation
A
Invagination of the Neural Plate to form a Neural Groove with Neural Folds on either side.
3
Q
Neural Crest
A
Forms from Surface Ectoderm while the Neural Tube is detaching from the Surface, giving rise to the Peripheral Nervous System
4
Q
Neural Tube Progressive Development
A
WALLS (CRANIAL 2/3):Thicken to form the Brain
WALLS (CAUDAL 1/3): Thicken to form the Spinal Cord
LUMEN - Forms the Ventricular System of the Brain and Central Canal of the Spinal Cord
5
Q
Dilations of Primordial Brain
A
Prosencephalon - Forebrain
Mesencephalon - Midbrain
Rhombencephalon - Hindbrain
6
Q
Primordial Brain Structures, Associated Secondary Structures, and Adult Derivates of Walls and Cavities
A
7
Q
Flexures of the Primordial Brain
A
- Cephalic (mesencephalic) flexure – forebrain rotates ventrally and posteriorly
- Cervical Flexure – Demarcates cervical S.C. & brainstem
- Pontine Flexure – Reverse dorsal flexion
8
Q
Prosencephalon (Forebrain) Gives Rise To
A
Telencephalon (Endbrain) and two lateral outpocketings that from the Primitive Cerebral Hemispheres
Diencephalon (Outgrowth of the Optic Vesicles)
9
Q
Rhombencephalic Isthmus
A
Separates the Mesencephalon from the Rhombencephalon
10
Q
Pontine Flexure
A
Separates the Rhombencephalon into the Metencephalon and the Myelencephalon
11
Q
Metencephalon
A
Forms the Pons and Cerebellum
12
Q
Neuroepithelial Cell Differentiation Tree
A
Neuroepithelial Cells → Neuroblasts (1st) + Glioblasts (2nd) + Ependymal Cells (3rd)
Neuroblasts → Neurons
Glioblasts → Astroblasts (Fibrous and Protoplasmic) + Oligodendroblasts
13
Q
(Ependymal) Ventricular, Mantle and Marginal Zones
A
VENTRICULAR (EPENDYMAL) - Innermost layer formed by Neuroepithelial Cells
MANTLE - A zone formed by Neuroblasts around the Epithelial layer that will give rise to the Gray Matter of the Spinal Cord
MARGINAL - Outermost layer of the Spinal Cord that contains the nerve fibers emerging from the Neuroblasts in the Mantle Layer
14
Q
Glioblasts
A
Formed from differentiated Neuroblasts that migrate from the Ventricular Zone into the Mantle and Marginal Layers. Gives rise to Astroblasts and Oligodendroblasts
15
Q
Astroblasts
A
Formed from the Glioblasts and found in the Mantle and Marginal layer. Will give rise to both Fibrous and Protoplasmic Astrocytes
16
Q
Oligodendroblasts
A
Formed from the Glioblasts and found in the Marginal layer forming Myelin sheaths around the ascending and descending axons.
17
Q
Ependymal Cells
A
Ependyma of the Ventricular Zone that line the Central Canal of the Spinal Cord.
These differentiate from Neuroepithelial cells once Neuroblasts and Glioblasts have ceased formation
18
Q
____________ senses molecular markers that guide axons to the correct route
A
Growth cone
19
Q
Guidance of Growth Cone
A
The axon travels through the Extracellular Matrix, guided by both Diffusible and Non-Diffusible signals
20
Q
Netrins/DCC (Chemo-Attractant/ Chemo-Repellent)
A
Chemo-Attractants
21
Q
Slit/Robo (Chemo-Attractant/ Chemo-Repellent)
A
Chemo-Repellents that prevent an axon from straying back over the midline once the axon has passed the midline in reponse to Netrin
22
Q
Semaphorin/Plexin (Chemo-Attract/ Chemo-Repellent)
A
Chemo-Repellents that prevent the lateral extension of the nearby axons and cause lateral collapse of growth cones
23
Q
Basal vs Alar Plates
A
BASAL - Ventral thickenings that contains the Ventral Motor Horn Cells (becomes the ventral horn)
ALAR - Dorsal thickenings that form the Sensory (Afferent) Areas (becomes the Dorsal Horn)
24
Q
Sulcus Limitans
A
Marks the boundary between the Basal and Alar plates
25
Roof/Floor Plates
Midlines portions of the neural tube that do not contain Neuroblasts but serve as pathways for nerve fibers crossing from one side to the other
26
Metencephalon Derivatives
The Metencephalon will give rise to the Pons and Cerebellum
27
Cerebral Aqueduct
Forms form the narrowing of the Neural Canal and functions to connect the Third and Fourth Ventricles
28
Ectoderm
CNS, PNS, epidermis, sensory organs
29
Mesoderm
skeletal system, muscles, connective tissues, dermis, vascular region
30
Endoderm
Gut, lungs, liver
31
Phase I: Primary Neurulation
Neural crest cells:
Group of cells from crest of each neural fold "pinched off" during formation of neural tube
differentiating into:
• Ganglia of sensory neurons of spinal nerves (DRGs), and cranial nerves
• postganglionic neurons of Autonomic nervous system
(autonomic ganglia)
• Schwann cells and satellite cells of PNS.
• Endocrine organs (adrenal
medulla)
• Leptomeninges: pia & arachnoid connective tissue of CNS
32
Phase II: Neural Tube Differentiation
Secondary Neurulation
Closed neural tube separates into 2 distinct layers
( ~Day 26)
-Mantle layer: ‐ the inner ring
cell bodies grey matter
-Marginal layer: the outer ring
axons white matter
-Ependymal layer: the inner most ring
cells line ventricles, etc.
33
Midbrain fate
remains the midbrain
cavity becomes cerebral aqueduct connecting the 3rd and 4th ventricles within the midbrain region
34
Hindbrain (rhombencephalon) fate
Metencephalon
--becomes pons, medulla, cerebellum and part of 4th ventricle
Myelencephalon
--becomes lower medulla
part of 4th ventricle and part of central canal
35
What happens when cranial neural tube fails to fuse properly?
Anencephaly
36
Arnold-chairi Malformation
Developmental deformity of hindbrain
Types:
• Type I: herniation of cerebellar
tonsils through foramen magnum
into central canal; pons & medulla
smaller and malformed
• Type II: brainstem & cerebellum
malformed and pushes down into
foramen magnum
• Hydrocephalus requiring
shunting in ~ 90%
• Associated with spinal bifida
37
Meningocele
failed vertebral column formation resulting in sac-like protrusion of membrane- no neural tissue
38
myelomenigocele
Failed vertebral column formation resulting in sac‐like protrusion of membrane with protrusion of spinal cord and membrane
39
Thoughout the primitive streak and node, the cells that make up this area are prolifereating and migrate to different areas of the embryo. The ones that migrate through the primitive streak and node ___________ are important because they give rise to the notochord and the CNS.
Rostrally
40
How is right and left symmetry formed?
* The cells that form the notochord (mesoderm) go through the primitive node and go through a period where they fuse with the encoders (ectoderm) and become a rod that forms the axis that forms left and right symmetry.
* Basically the mesoderm-forming somites and the overlying ectoderm take to each other.
* They send signals that go back and forth to each other so that the NS forms in conjuction with the segmentation of the body.
41
What are the derivatives of the mesoderm? What does each derivative form? Where is each located in relation to the midline?
**Paraxial Mesoderm**
* **Closest to midline (medial)**, thick
* **Forms somitomeres** which give rise to mesenchyme of head and organize into somites at occipital and caudal levels – vertebral column, limb, body wall musculature
**Intermediate**
•Urogenital system
**Lateral Plate Mesoderm**
* Thin, **lateral**
* line peritoneal, pleural and pericardial; thin membrane around each organ, vessels,etc.
42
The notochord has a ________ axis of formation.
Cranial-Caudal
43
The notochord is important in establishing the body's ____________ axis.
Longitudinal
44
\_\_\_\_\_\_\_\_\_\_\_ induces columanr epithelial cells above to become the neural plate.
Notochord
\*The notochord secretes molecules that induce the overlying ectoderm to become the neural plate
45
What is the first event in formation of the nervous system? One what day does this take place?
**Formation of the neural plate. Induction of the neural plate occurs on E18**
NOTE: Proliferation of somites occurs along with the development of the neural plate and neural groove. So, by the tume we are at day 22, we can see the future forebrain, midbrain, and hindbrain
46
How does induction of the neural plate take place?
The neural plate forms in response to signals (**inducers**) from notochord/mesoderm (**organizers).**
**NOTE**: The organizing capacity of the notochord/mesoderm begin at a point prior to gastrulation. The organizers induce change with contac.
47
What is the **ventralizing** signal for intermediate mesoderm and lateral mesoderm? How are axes established?
Bone Morphogenetic Protein-4 (BMP-4)
\*BMP-4 is antagonized by **chordin, noggin, and follistatin.**
**NOTE:** Whent this antagonism happens, the mesoderm that is migrating through there becomes **dorsalized** rather than becoming lateral or intermediate mesoderm.
48
Chordin, Noggin, Follistatin antagonize actions of ________ and \_\_\_\_\_\_\_\_\_\_\_.
BMP-4 (induces **ventral orientation)** &FGF.
49
The absence or inactivation of BMP-4 induces what two actions?
* Ectoderm becomes **neuralized**
* Mesoderm becomes **dorsalized**
50
In the node, mesoderm that has been dorsalized becomes what?
Notochord, somites, and somitomeres
51
In the notochord, induction of overlying ectoderm to become neuralized promotes formation of what?
Midbrain and forebrain
52
Do cranial and caudal neural plate structures depend on the same secreted proteins for induction?
NO.
The **cranial** structures require **BMP-4, and chordin, noggin, and follistatin**, as antagonizers.
The **caudal** structures require **BMP-4, and Wnt-3a and FGF**, as antagonizers.
\*This is how the spinal cord forms instead of the brain or visca versa.
53
What are the caudal neural plate structures?
Hindbrain and spinal cord
54
•\_\_\_\_\_\_\_\_\_\_\_ from notochord sets up the neural groove/midline.
Sonic hedgehog (SHH)
55
•\_\_\_\_\_\_\_\_\_\_\_\_ also an important organizer – regulates homeobox (HOX)gene expression in hindbrain.
Retinoid acid
56
Sonic hedgehog blocks \_\_\_\_\_\_\_\_\_
BMP-4
57
The neuralation gives rise to the CNS from the ____________ to the _________ regions of the spinal cord.
Prosencephalon; lumbar
58
Which end of the neural tube closes first?
The cranial neurotube end closes first on day 24 and the caudal end closes on day 26.
59
On day 22, the neural plate creases ventrally at midline, the lateral lips of the folds meet to form a tube called the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.
Neural canal
60
A transcient migratory group of cells that emerge from the dorsal lip of the neural tube.
Neural crest cells.
\*Neural crest cells are transcient so they migrate deep as well as superficially to give rise to things like the adrenal gland, DRG, parts of the eye, etc.
61
How is the fate of neural crest cells determined?
By local environment
\*Neural crest cells won't migrate anteriorly or posteriorly for the most part, they will migrate at the level that they are generated.
62
What are the neural crest cell derivatives?
Neuronal Derivatives
•Ganglia of the PNS
–Dorsal Root Ganglia
–Autonomic Sympathetic Chain Ganglia
–Parasympathetic ganglia (of CN VII, IX, X)
–Cranial Nerve ganglia -- sensory ganglia of the CNs V, VII, VIII, IX, X
* Neural-like cells of the adrenal medulla.
* Schwann cells and satellite cells of DRG.
* The pia and arachnoid membrane coverings of the brain and spinal cord.
63
What are non neural derivatives of the neural crest cells?
* Odontoblasts
* Connective tissue around eye and around papillary and ciliary muscles, and many other nonneuronal tissues in the head.
* Melanocytes
64
Primary neuralation vs. secondary neuralation
Primary neuralation= the neural plate creases inward until the edges come in contact and fuse
Secondary neuralation= Tube forms by hollowing out of the interior of the solid precursor
65
What does the caudal eminence generate?
* The inferior sacral and coccygeal levels of the spinal cord
* Meninges
66
Neural tube from closure of neural pore ends at somite \_\_\_\_\_\_. The secondary neurulation process generates neural tube to somite \_\_\_\_\_\_.
31; 37
67
What are the risk factors for neural tube defects?
Alcohol
Diabetes
Folic acid deficiency
68
What are the wo types of spina bifida cystica?
Meningocoele
Meningomyelocele (more severe)
69
Raschischisis
Neural induction failed to occur. There was no induction for the neural ectodem. No neural tube formed, so no spinal cord formed at all
70
Holoprosencephaly
* Refers to a spectrum of malformations in which **loss of midline structures results in malformations of the brain and face**
* Craniofacial anomaly - lack of formation of the prosencephalon (forebrain)
* Frontonasal, midfacial structures and the forebrain are deformed.
* **Due to mutations in SHH or cholesterol metabolism.**
* Smith Lemli Opitz Syndrome(SLOS) – 5% of cases have holoprosencephaly.
* Due to teratogens such as alcohol, which selectively kills midline cells during early stages of development –Thus, inhibit induction of the prosencephalon.
* HPE 1/15,000 live births, but 1/250 miscarriages
71
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ metabolism is involved in sonic hedgehog mechanisms.
Cholesterol
72
Where is alpha-fetoprotein synthesized and where is it found?
–synthesized in the liver and is a major component of fetal serum.
73
Alpha-fetoprotein is increased in cases of...
Neural tube defects
Cancer (liver, testiculr, ovarian)
74
Alpha-fetoprotein is decreased in cases of...
Chromosomal disorders, such as Down's syndrome
75
The mechanisms of brain expansion are seen in 3 and 5 vesicle stages. What are the components of the 3 (primary) vesicles stage? What are the components of the 5 (secondary) vesicles stage?
_3(primary)_
* Forebrain (prosencephalon)
* Midbrain (Mesencephalon)
* Hindbrain (Rhombencephalon)
_5(secondary)_
* Telencephalon
* Diencephalon
* Mesencephalon
* Metencephalon
* Myelenocephalon
76
What are the adult derivatives of the telencephalon?
* Olfactory lobes
* Hippocampus
* Cerebrum
77
What are the adult derivatives of the mesencephalon?
Midbrain
78
What are the adult derivatives of the diencephalon?
* Retina
* Epithalamus (Pineal gland)
* Thalamus
* Hypothalamus
79
What are the adult derivatives of the metencephalon?
* Cerebellum
* Pons
80
What are the adult derivatives of the myelenocephalon?
* Medulla
81
The ___________ becomes the optic nerve.
Optic stalk
82
Hydrocephaly
- Results from **blockage of ventricular flow** (usually at the **cerebral aqueduct in the mesencephalon**; foramina of Luschka and Magendi in the 4th ventricle)
## Footnote
**-Causes an enlargement of the lateral ventricles and a thinning of the cerebral cortex**
83
There is a hollow portion inside the brain flexure. What does that hollow portion become?
The ventricles
84
List the seconday organizers of the neural tube
1. Anterior neural ridge
2. Zona limitans intrathalamica (ZL1)
3. Isthmic organizer (IsO)
4. BMP4, 7
85
Which secondary organizer is important to the patterning of the mesencephalon and the cerebellum?
Isthmic organizer
\*Demarcates where the mesencephalon ends and the metencephalon begins. All it is is a strict layer of expression of Wnt and FGF8.
86
Which secondary organizer helps with the segmentation of the thalamus?
Zona limitans intrathalamica
\*Found in the middle of the diencephalon
87
Which secondary organizer is the organizer of the anterior prosencephalon?
Anterior neural ridge
\*Found at the anterior end of the neural plate. It secretes Fgf8, which can impart anterior properties, induces expression of Brain factor 1 (BF1)
88
What are the segments of the hindbrain called?
Rhombomeres
\*Each rhombomere has a unique identity with characteristic cell types. They have restricted expression of homeobox genes, and the complement of Hox genes define specific segments
89
Stem cells in the adult brain are found near the ____________ layer.
Ependymal
90
As make neurons, the 1st set of cells that are going to be made from the neuroepithelium are going to be called \_\_\_\_\_\_\_\_\_\_.
**Neuroblasts**
\*This means that they have the **potential** to become neurons, but they are pluripotent.
91
92
In neurogenesis, after you generate the cells, most cell bodies are going to live where? What about the axons?
Cell bodies: Mantle layer
Axons: Marginal layer
93
What the steps to dorsoventral pattering?
1. The notochord induces a floor plate.
2. The floor plate along with the sonic hedgehog gene send signals that tell the cells that are closest to the floor plate to adapt a motor fate and those that are far will adapt a more sensory fate.
* At this stage the cells that adapt a motor fate are called basal plates and those that adapt a sensory fate are called alar plates.
3. The BMPs and the roof plate also induce dorsal cell trypes in neural tube.
94
Which cells form the wall of the neural tube?
Neuroepithelial cells
95
How does the development of the brainstem/medulla differ from that of the spinal cord?
_Brainstem/Medulla_
* Stretched roof plate- dorsal midline of neural tube, forms roof the **4th ventricle** in medulla
* **Medial** basal plate- ventral; motor
* **Lateral** alar plate- dorsal; sensory
_Spinal Cord_
* Roof plate not stretched
* Dorsal- sensory
* Ventral- motor
96
Development of which structure requires more rounds of neuroblast differntation
Forebrain/ Cereral Cortex
\*•More rounds of neuroblast differentiation to generate multiple (II-VI) layers of neurons in cortex.
97
What are the characteristics of forebrain/ cerebral cortex development?
* Similar to development of spinal cord and brain stem EXCEPT
* **More rounds of neuroblast differentiatio**n to generate multiple (II-VI) layers of neurons in cortex.
* **Inside-out pattern of lamination**
* Layers formed 1,6,5,4,3,2
* More complex organization and function.
* **Grows out of ventricular zone proliferations** (radial migrations)
* **Layer IV is special**… it receives its GABA-ergic neurons from the medial ganglionic eminence
* **Tangential migrations**
98
What is unique about layer 4 of neurons in the cerebral cortex?
* It undergos tangetial migrations
* It receives its GABA-ergic neurons from the medial ganglionic eminence
99
What is radial migration?
Cerebral cortical neurons are generated in the ventricular zone and migrate along radial glia, settling in an inside-out fashion.
100
What is tangential migration?
* Neurons born in the **Medial Ganglionic Eminence (MGE)** travel **far from the site of their birth** to reside in Layer IV of the cerebral cortex – give rise to interneurons
* **Lateral Ganglionic Eminence (LGE)** neurons migrate to olfactory cortex and bulb
* **Rostral Migratory Stream** – neurons migrate from the Subventricular zone to olfactory bulb
101
Lissencephaly
Gyri don't form.
102
Which molecules are involved in contact-mediated attraction, in axon outgrowth?
* IgCAMs
* Extracellular matrix molecules
* laminin
* fibronectin
103
Which molecules are involved in long range attraction, in axon outgrowth?
* netrin
* neurotrophins
* slits
104
Which molecules are involved in long range repulsion, in axon outgrowth?
* semaphorins
* slits
* netrin
105
Which molecules are involved in contact-mediated repulsion, in axon outgrowth?
* ephrins
* transmembrane semaphorins
* ECM molecules
* tenascin
* CSPGs
106
How does a cell that is born come down to where motor neurons are, cross the midline and then go rostrally?
The floor plate is expressing an attractive cue that is attracting this axon toward it.
\*Axons that cross the midline are called **commisural axons**
107
What molecule binds to DCC (deleted in colorectal cancer) and induces a favorable cue?
Netrin
108
What happens once commissural axons cross the midline?
It will express ROBO.
\*This is understood because when robo is knocked out the axon doesn't stay where it needs to , it goes everywhere and anywhere.
**NOTE:** When the axon expresses ROBO it will respond to the repulsive cue of _slit_ and actually ROBO silences DCC's ability to respond to nectrin. That's what keeps it from going back to the other side, and keeps the axon remaining crossed
109
What causes the agenesis of the corpus callosum?
* When the commissural axons can't cross the midline, you hvae agenesis of the corpus callosum so you aren't going to ave any communication between the left and right brain
