Q3: Neurology: Embryology Of The Brain And Construction Of Neural Circuits

Front 1

BASAL PLATE

Back 1

The ventral part of the neural tube that becomes the motor part of the nervous system.

Front 2

ALAR PLATE

Back 2

The dorsal part of the neural tube that becomes the sensory part of the nervous system

Front 3

FLOOR PLATE

Back 3

The ventralmost part of the neural tube.

Front 4

TGF- beta

Back 4

The embryonic structure immediately ventral to the neural tube.

Front 5

NOGGIN AND CHORDIN

Back 5

Secreted by the basal plate and notocord. These inhibit BMP to allow the neural tube to form and also promote the development of the basal plate
of the neural tube.

Front 6

NOTCH AND NUMB

Back 6

Numb antagonizes notch effect on gene transcription. As long as notch is suppressed, the cell keeps replicating. When notch dominates, the cell stops dividing.

Front 7

NOTCH AND DELTA

Back 7

Delta, expressed on a cell surface interacts with notch on the adjacent
cell, which inhibits delta expression in that cell. This results in adjacent cells
having high levels of notch and delta. High notch results in a glioblast, high delta
results in a neuroblast. Therefore, glia and neurons are intermixed.

Front 8

BASIC HELIX- LOOP-HELIX GENES

Back 8

Activation of these genes contributes to development of a neuron.

Front 9

GROWTH CONE

Back 9

Activation of these genes contributes to development of a neuron.

Front 10

LAMELLOPODIA

Back 10

Flattened part of the growth cone.

Front 11

FILOPODIA

Back 11

“Fingers” extending from the growth cone, sampling the environment.

Front 12

LAMININ

Back 12

Extracellular matrix protein that interacts with integrins in the filopodia.

Front 13

INTEGRIN

Back 13

Cell surface protein that interacts with extracellular matrix (especially laminin)
and also with intracellular signaling molecules to promote outgrowth.

Front 14

CELL ADHESION MOLECULE (CAM)

Back 14

Many splice isoforms thainteration (in this case, between growing neuritis).

Front 15

CADHERIN

Back 15

Calcium dependent interaction molecules for direct cell-to-cell interaction.

Front 16

CHEMOATTRACTANT

Back 16

A molecule that results in attraction of a growing axon.

Front 17

CHEMOREPELLENT

Back 17

A molecule that results in repulsion of a growing axon.

Front 18

PINOEER AXON

Back 18

The first-arriving axon, which other axons in the pathway follow.

Front 19

FASCICULATION

Back 19

The guidance of growth of adjacent nerve processes along the course of adjacent ones (through cell adhesion molecules)

Front 20

NETRINS

Back 20

Chemoattractive for growing axons that express Netrin receptors.

Front 21

SLIT

Back 21

A repulsive factor on a growing axon (works by interacting with a receptor, Robo.

Front 22

EPHRINS

Back 22

A family of proteins that interacts with receptors (eph) on a growing fiber. Eph
contains a tyrosine kinase function and can be attractive or repellent.

Front 23

SEMAPHORIN 3A

Back 23

Diffusible protein manufactured by cells in cortical layer I that attracts dendrites of pyramidal cells and repels their axons.

Front 24

AGRIN

Back 24

Protein secreted by growing motor axon that interacts with muscle-specific kinase (MuSK) in muscle membrane. This results in activation of rapsyn, which causes expression of acetylcholine receptors.

Front 25

NEUROGLIN

Back 25

Made by the axon terminal at the neuromuscular junction. This results in increased expression of acetylcholine receptors.

Front 26

NOGO

Back 26

Prevents neurite outgrowth. Is at least one factor inhibiting repair of CNS axons.

Front 27

NERVE GROWTH FACTORS

Back 27

A family of proteins that work to switch off cell death program
(i.e., prevent apoptosis) via interaction with trk (tyrosine kinase) receptors.

Front 28

What are the 3 germ layers and what do they form?

Back 28

1) ECTODERM
skin, skin appendages, hair, lens, iris, cornea and inner ear
Neural plate - neuroectoderm
Will form the neural tube

2) MESODERM
connective tissue, muscle (all kinds), blood vessels, blood and urogenital system

3) ENDODERM
digestive and respiratory systems

Front 29

What 8 things occur in NEURULATION?

A) What different tissues thicken? (2)

B) When do the neural folds fuse to form the tube?

C) What does the lumen become? (2)

Back 29

A)
1) Thickening of ectoderm (neuorectoderm) forms neural plate

2) Thicken and form a pseudostratified columnar epithelium

B) Edges have increased growth and form folds

This leads to groove (neural groove)

Folds fuse to form tube (fusion begins at day 21) and it starts at 4th somite and goes rostrally and caudally

Anterior and posterior neuropores

C) Lumen becomes the ventricle system and central canal of spinal cord.

Front 30

What is SPINA BIFIDA?

Back 30

This is a deficit in the structures covering the inferior portion of the spinal cord and cauda equina

If there is just deficient mesoderm covering the dorsal aspect then can get spinabifida occulta

Front 31

When do you get a MENINGOCELE?

Back 31

If neural crest tissues are deficient

Front 32

When do you get a RACHISCHISIS?

Back 32

If neural tube doesn't close (in posterior neuropore)

Front 33

Where are the NEURAL CREST CELLS in relation to the NEURAL TUBE?

Back 33

They are the cells at lip of neural tube as it closes

Front 34

What are the two types of cells that NC develop into?

Back 34

NEURONAL

NON NEURONAL

Front 35

What are the NEURONAL developments? (4)

Back 35

1) Dorsal root (spinal) ganglia and all sensory nerve fibers

2) Ganglia of cranial nerves

3) Autonomic gangli

4) Adrenal medulla

Front 36

What are the NON NEURONAL developments? (3)

Back 36

1) Schwann cells and satellite cells

2) Leptomeninges (pia/arachnoid)

3) Bone and connective tissues of the face and skull base

Front 37

BRAIN VESICLES:

What are the PRIMARY BRAIN VESICLES? (3)

A) When do they start to develop?

B) What do each of the vesicles develop into?

Back 37

A) Begin to develop after the neuropore closes at day 25

B)

1) RHOMBENCEPHALON- most caudal
a) MYLENCEPHALON- medulla
b) METENCEPHALON- pons and cerebellum

2) MESENCEPHALON
a) MIDBRAIN

3) PROSENCEPHALON
a) DIENCEPHALON- thalamus
b) TELENCEPHALON- cerebral cortex and basal ganglia

Front 38

What are teh 3 BRAIN FLEXURES and where are they located?

Back 38

1) Cervical flexure
Spinal cord - rhombencephalon
juncture

2) Pontine flexure
Dorsal fold at mylencephalon/ metencephalon junction

3) Cephalic flexure
At mesencephalon

Front 39

HISTOGENESIS:

A) What is the cell structure of the NEURAL TUBE?

B) Where does cell nuclei move frokm?

C) Where does DNA synthesis occur?

D) Where does NUCLEUS migrate towards?

Back 39

A) Neural tube initially pseudostratified columnar

B) Cell nuclei move from near internal limiting membrane to external limiting
membrane

C) DNA synthesis occurs when nucleus near external limiting membrane

D) Nucleus migrates toward internal membrane and cell divides
Eventually no longer synthesize DNA (postmitotic)

NOTE: We now know that some neurons maintain the ability to divide later in life but it
is not known how important or functional these neurons are

Front 40

MIGRATION:

A) What are the 3 layers of the CNS?

B) Where do NEUROBLASTS migrate from?

C) What does the MANTLE ZONE become?

D) What does the MARGINAL WHITE ZONE become?

E) Where do GLIOBLASTS migrate and whta do they become?

Back 40

A) Ventricular zone, intermediate (mantle) zone and marginal zone

B) Neuroblasts migrate from the ventricular zone to mantle zone

C) Neuroblasts send axons into the marginal zone

D) Mantle zone becomes gray matter and marginal zone white matter

E) Glioblasts migrate and become astrocytes or oligodendrocytes

Front 41

What are RADIAL GLIA and what is their function?

Back 41

Early in development, some glial cells maintain connection with the internal and external limiting membrane

These provide guidance to migration

Front 42

A) What is the CEREBRAL CORTEX?

B) What is the OLDEST/ YOUNGEST layer?

C) What is SEMAPHORIN A?

Back 42

A) Successive waves of migration from ventricles to reach Layer I (the oldest layer)

B) Therefore, layer VI is next oldest and layer II is the youngest layer
The thalamic connections grow into the cortex and determine what kind of cortex
it will become (sensory, motor, association, etc).

C) SEMAPHORIN A is diffusible molecule created in Layer I. This attracts dendrites of
pyramidal cells and repels the axon (leads to charpyramidal cells)

Front 43

What are MICROGLIAL CELLS?

Back 43

These are mesodermal

Migrate into neural tube are derived from macrophages

Front 44

What are GLIOBLASTS?

Back 44

These differentiate quite late (oligodendroglia last – myelination is a late process)

Front 45

What are EPENDYMAL CELLS?

Back 45

Glial cells that do not migrate from ventricular zone

Line the lumen of the tube

Front 46

FACTORS DETERMINING CELL AND NEURONAL FATE:

A) Where are FACTORS that determine if a NERUAL TUBE will develop located?

B) What do factors DIFFERENTIATE?

C) What do DIFFUSIBLE compounds determine?

Back 46

A) Factors determine if a neural tube will develop from ectoderm
Must inhibit BMPs by presence of noggin and chordin

B) Factors differentiate ventral from dorsal part of the neural tube
Sonic hedgehog ventrally, TGF betas dorsally (BMP, dorsalin, vit A)

C) Diffusible compounds determine level of the brain stem that will develop from a
particular part of the neural tube

Front 47

What is RETINOIC ACID an example of?

Back 47

* see notes

Front 48

What factors determine whether a cell will become a NEURON or GLIAL CELL?

Back 48

1) Notch (interacting with delta) will prevent cells from becoming neuroblasts.

2) Basic Helix-Loop-Helix genes activated in neuroblasts

*NOTE: There are factors that determine the fate of a cell as it develops.

Cells are affected by the milieu through which they migrate.

Front 49

What are the 3 important factors in wiring of the brain?

Back 49

1) PATHWAY SELECTION

2) TARGET SELECTION

3) ADDRESS SELECTION

Front 50

1) PATHWAY SELECTION

Back 50

• Fundamentally, there are forces on growth cone. This cone puts out filopodia
from the lamellopodia.

• Attractants result in polymerization of actin and later of tubulin.

• Repellents result in depolymerization of actin.

• There are chemoattractive and repulsive soluble compounds. There are receptors
for these compounds that are linked to intracellular mechanisms that result in the
stabilization or destabilization of processes.

• A classic example is the decussation of spinothalamic tract. Growth cone makes
netrin receptors that are attracted by netrin in the floorplate. The axon grows to
the floorplate where the high concentration of netrin causes upregulation of Robo receptors (and downregulation of netrin receptors). There is also high concentration of slit in the floorplate that is chemorepulsive to axons containing
Robo. Therefore, the axons do not recross.

• The decussation of nasal, but not temporal fibers at the optic chiasm results from
expression of eph receptors on the temporal optic nerve fibers that are repelled by
the particular ephrin made by glial cells of the optic chiasm.

• Axons are guided along pioneer fibers by interaction with adjacent fibers through
cell adhesion molecules. These result in “fasciculation” (i.e., the tendency of
fibers to clump together in tracts).

Front 51

2) TARGET SELECTION

What does it involve?

Back 51

• It involves specific recognition molecules and “directions” in the environment

• Gradient of ephrins (interacting with eph receptors on the growing axons) are important in topographic termination of visual inputs to frog superior colliculus

Front 52

3) ADDRESS SELECTION

What does this result in?

What is AGRIN?

What promotes ACH receptor expresssion?

Back 52

• ADDRESS SELECTION of synapses result from interactions between the growing axon and its target.

• This is most well known for the neuromuscular junction.

• Agrin is a protein secreted by growing motor axon. This interacts with muscle-
specific kinase (MuSK) in muscle membrane, resulting in activation of rapsyn.
This causes aggregation of acetylcholine receptors in the muscle membrane.
Acetylcholine receptor expression is promoted by neureglin, which is also made by the axon terminal.

Front 53

ADDRESS SELECTION CONT...

How are neurons prevented from undergoing PROGRAMMED CELL DEATH?

Back 53

•This occurs through interaction between nerve growth factors (many varieties) and tyrosine kinase (trk) receptors.

Front 54

What is the significance of ACTIVITY- DEPENDENT PLASTICITY?

Back 54

• Both the amount and the quality of the synaptic input can result in stabilization of
a synapse. The precise signals are not known, but appear to involve metabotropic
receptors (through second messenger mechanisms) and calcium-dependent
mechanisms at the level of the synapse.

• There are critical periods in which this happens in most pathways (best shown inthe visual system).