Development of the Nervous System (Prof Price)

Question 1

What are the 3 main functions of the nervous system ?

Answer 1

Sensation, integration and initiation of motor activity.

Question 2

What is the role of the CNS (brain + spinal chord) ?

Answer 2

• Receives sensory information Integrates
• Generates motor activity
• Controls consciousness and perception

Question 3

What is the role of the PNS (all nerves and ganglia outside brain and spinal chord) ?

Answer 3

Carries sensory information to CNS from periphery (via afferent nerves)
Carries motor information from CNS to periphery (via efferent nerves)

Question 4

Wha are ganglia ?

Answer 4

Ganglia are collections of nerve cell bodies.

Question 5

How many spinal nerves supply the trunk and limbs ?

Answer 5

32 pairs:

• 8 cervical
• 12 thoracic
• 5 lumbar
• 5 sacral
• 1 coccygeal

Question 6

How many cranial nerves are there ?

What do they control ?

Answer 6

The 12 cranial nerves control many neck and head functions (but not only e.g. X (vagus) controls intestines).

Question 7

How do white and get matter proportions vary in the spinal chord ?

Answer 7

At the top of the spinal chord (cervical level), white matter is more abundant because the fibers innervating the whole body progressively join up until they reach C1 (so the axons add up).

Question 8

What does the diencephalon contain ?

Answer 8

The thalamus and the hypothalamus.

Question 9

What does the brainstem contain ?

Answer 9

The midbrain, the pons and the medulla.

Question 10

How does the brain change during development ?

Answer 10

The CNS develops initially as a simple hollow tube.
The cerebral hemispheres develop as outgrowths on either side from the cranial end of this tube.
As they grow they sweep back over the surface of the tube “hiding” the central core of the developing brain.

Question 11

What did Samuel Taylor Coleridge say about developmental biology in 1803 ?

Answer 11

“The history of man for the nine months preceding his
birth would be far more interesting and contain events of greater moment than all threescore and ten years that follow it.”

Question 12

What did comparative embryologists, such as Pander (1794-1865), von Baer (1792-1876), and Rathke (1793-1860), recognize concerning embryonic development ?

Answer 12

That different species undergo similar stages of development.

Question 13

What are the steps between fertilization and formation of a larva.

Answer 13

Fertilization is followed by cleavage divisions that break up the large egg into smaller cells, creating a fluid filled sphere called the blastula. The multilayered structure of the larva is created by a coordinated series of cell movements called gastrulation. At this point the three germ layers (ectoderm, mesoderm and endoderm) become apparent, which subsequently form the tissues..

Question 14

Which scientist discovered germ layers ?

Answer 14

Christian Pander (1794-1865) while studying chick embryos.

Question 15

What are the characteristics of germ layers ?

Answer 15

They are found in all triploblastic embryos and each germ layer forms similar tissue types in all animals. Some phyla, such as porifera (sponges), cnidarians (sea anemones, hydra, jellyfish) and ctenophors (comb jellies) lack true mesoderm and are considered diploblastic animals. Germ cells (future gametes) are classified separately.

Question 16

What is differentiation ?

Answer 16

The process whereby cells acquire their functional characteristics.

Question 17

Quote a scientist that illustrates the physical similarity of certain embryos.

Answer 17

“I have two small embryos preserved in alcohol, that I forgot to label. At present I am unable to determine the genus to which they belong. They may be lizards, small birds, or even mammals.” Karl Ernst von Baer (1828)

Question 18

What experiment did Hans Spemann (1869-1941) & Hilde Mangold (1898-1924) carry out in 1924 that revealed the principle of neural induction ?

Answer 18

Shaman and Mangold transplanted the prospective
notochord of a newt gastrula into the opposite side of a similarly staged host. They used newt species with different levels of pigmentation so that they could follow the transplanted cells. Remarkably, a conjoined twin was formed in which the transplant formed the notochord and parts of the nervous system. However, most of the nervous system was formed by host cells that would otherwise have formed epidermis. Thus the transplant has changed the fate of host cells from epidermis to neural. Only the propsective notochord could induce a conjoined twin and Spemann coined the term “organizer” to describe this region of the amphibian gastrula.

Question 19

How does the dorsal mesoderm migrate during gastrulation ?

Answer 19

During gastrulation the dorsal mesoderm (notochord) migrates anteriorly beneath the dorsal ectoderm, releasing “signals” that induce the nervous system. In the absence of these signals the dorsal ectoderm will form epidermis. In Spemann & Mangolds experiment, dorsal mesoderm was introduced on the ventral side of the embryo, inducing a second nervous system in the ventral ectoderm.

Question 20

What is induction ?

Answer 20

The process whereby a cell or tissue signals to another cell or tissue in the embryo, thereby affecting the development of the responding cell or tissue.

Question 21

What is competence ?

Answer 21

The ability of a cell or tissue to respond to an inducing signal - embryonic tissues only remain competent for a limited period of time.

Question 22

From what germ layer does the NS derive ?

Answer 22

The ectoderm.

Question 23

What is neurulation ?

Answer 23

The process of how the ectoderm begins to give rise to the Nervous System. It happens when the notochord instructs the ectoderm to form the rural tube.

Question 24

Are the CNS and PNS formed together ?

Answer 24

No, they are formed separately.

Question 25

What are the 3 different partitions of the ectoderm ?

What do these give rise to ?

Answer 25

• Outer ectoderm (epidermis): epidermis, hair, nails, sebaceous glands, olfactory epithelium, mouth epithelium (anterior pituitary, tooth enamel, cheep epithelium), lens, cornea
• Neural crest: PNS (schwann cells, neuralgial cells, sympathetic/parasympathetic NS, adrenal medulla, melanocytes, facial cartilage, dentine of teeth
• Neural tube: brain, neural pituitary, spinal chord, motor neurons, retina

Question 26

What are the 3 keys events of neurulation ?

Answer 26

1. Contact between notochord & future floor plate
2. Folding, delamination of neural crest
3. Closure, crest migration, roof plate formed, notochord separates

Question 27

What did Bror Rexed (1914-2002) identify in the early 1950s in the spinal chord ?

Answer 27

Rexed identified 9 distinct layers of cells within the spinal cord. Each of the layers contains neurons with specialised function

Question 28

What are the 4 stages that pluripotent ectodermal cells have to pass to become neural precursor cells or progenitor cells and then neurons ?

Answer 28

1. HaveCompetence:becoming progenitors
2. Specification: stay or leave from progenitor characteristics (intermediate; reversible)
3. Commitment (determination): entering neural differentiation pathway (neuronal subtype has been selected)
4. Differentiation:exitcellcycleand express neuronal genes

Question 29

Though what phases does the stem cell go through to become a differentiated cell ?

Answer 29

pluripotent stem cell –> committed stem cell –> progenitor cell –> differentiated cell(s)

Question 30

How did Alan Turing (1912-1954) define the morphogen in The chemical basis of morphogenesis (1952) ?

Answer 30

Truing defined a morphogen as a protein that gives positional information to cells via a concentration
gradient and alters cell fates.

Question 31

Define induction.

Answer 31

Induction is instructing the development of cells through the local communication among the embryonic cells.

Question 32

Lewis Wolpert coined the term “positional information” and defined the “French flag problem” - what did this mean ?

Answer 32

This meant that:
a) by some mechanism, morphogens elicit concentration-dependent responses from cells
b) The transplanted cells retain their identities (knowledge of which flag they belong to)
but also respect the positional effects of the host (ie their position within the other flag)

Question 33

How do we know that morphogens pattern the Neural tube (in the doors-ventral axis) ?

Answer 33

Evidence from delicate grafting experiments in chick embryos:

1. The notochord induce the floor plate
2. The floor plate will induce motoneurons

Question 34

What signaling molecule found in the notochord and floor plate radiates ventral induction ?

Answer 34

Sonic hedgehog (Shh).
Shh is the vertebrate homologue of the protein encoded by the Drosophila pattern-forming gene hedgehog.

Question 35

How does Shh act ?

Answer 35

In a concentration dependent manner:
10nm Shh: floor plate
1nm Shh: motoneurons

Question 36

What key signaling molecules patterns the roof plate and neural crest formation ?

Answer 36

Bone Morphogenic Proteins (BMPs) (but also WNTs, SLUG, LMX1A).

Question 37

What is the fate of the neural crest along the rostro-cudal axis ?

Answer 37

• Cranial: Connective tissue and skeletal contributions to the face
  Schwann cell
• Vagal: Enteric (gut) NS
• Trunk: Melanocytes, Sensory and Sympathetic ganglia, Schwann cells, Adrenomedullary cells
• Lumbo-Sacral: Enteric (gut) NS

Question 38

How do cells of the trunk crest migrate ?

Answer 38

• Neural crest cells destined to be melanocytes migrate dorsolaterally into the ectoderm and continue towards the midline
• Most neural crest cells pass ventrolaterally through the anterior half of each sclerotome
• Some remain in the sclerotome and become the DRGs
• Some continue forming the sympathetic ganglia and the adrenal medulla, and the nerve clusters surrounding the aorta

Question 39

What are the 3 types of neural crest cells that populations that form the Dorsal Root Ganglions (DRGs) ?

Answer 39

• one from the neural crest opposite the anterior portion of the somite
• one from each adjacent neural crest regions opposite the posterior portions of the somites.

Question 40

Which cells form the epinephrine secreting cells of the adrenal medulla ?

Answer 40

At specific regions of the trunk, neural crest cells aggregate to form the sympathetic ganglia and the epinephrine secreting cells of the adrenal medulla.

Question 41

When do glial cells differentiate ?

Answer 41

Glial cells differentiate fro neural crest cells after the neuronal component.

Question 42

When does the migration of schwann cell (SC) progenitors stop ?

Answer 42

When they encounter axons, whose signals tell schwann cells what to do.

Question 43

What are neuregulins ?

Answer 43

A family of peptides originally found as factors that stimulate the phosphorylation of the erbB-2 receptor (expressed by SC precursors). Multiple variant forms of neuregulins occur due to alternative splicing of their mRNAs. The neuregulins include products from the three known genes (NGR1; NGR2 and NGR3).

Question 44

Why are neuregulins important for SC differentiation ?

Answer 44

Neuregulins eg. glial growth factor (GGF) are expressed by motor neurons and in neurons of peripheral ganglia. These stimulate differentiation and proliferation of SC precursors, and also contribute to survival of SC precursors.