AMHERST COLLEGE

INTRODUCTION TO NEUROSCIENCE

MONDAY, FEBRUARY 4, 2008

DEVELOPMENT I: PROLIFERATION, MIGRATION

• Today’s reading: Neuroanatomy questions

Chap. 7(178- 1. What is an exception to the rule that “ganglia”
195); 23(690-698) are in the PNS?
• Wednesday: 2. Place in rostro-caudal order:
Chapter 23 (698- • Inferior colliculus
708) • Thalamus
• Medullary respiratory center
3. The “medial forebrain bundle” is, as the name
suggests, a bundle of axons in the medial
forebrain . Why isn’t it called the “medial
forebrain tract”?
 Tomorrow -

7:00 AM to 8:00 PM
Bangs Community Center
(Behind Panda East & Rao’s)
Outline of development
 Proliferation
Fertilized egg Whole organism
(single cell)
1011 neurons

Question: how many rounds of cell division?

2x2x2x2x…. = 10x10x10x….x10
Log10(2)=3.3, i.e.10 = 23.3, so 1011=(23.3)11= 236
 Early vertebrate development
Neural groove → neural tube. Vertebrate CNS = hollow organ

Neural crest:
-Dorsal root ganglia
-Autonomic ganglia
-PNS myelin

CNS

Notochord
Fig. 7.8
Vertebrate brain development: 3
subdivisions
Anterior neural tube → 3 brain ‘vesicles’

Basal Line of Thalamus

Fig. 7.9, 7.10, 7.13 ganglia “secondary
fusion”
 Development of the retina

Fig. 7.10,11

Retinal ganglion cells develop after the optic cup is formed. Their
axons grow from the retina to the diencephalon and midbrain.
Is “optic nerve” a consistent name for the bundle of axons
connecting the retina to the rest of the brain?
Is “ganglion” cell a consistent name for neurons in the retina?
 Features of proliferation
• Cell divisions occur in
ventricular zone

• Nucleus moves to
marginal zone for “S”
phase (synthesizing
DNA for next division)

• Cell becomes
postmitotic (has its
“birthday”) after
horizontal cleavage
Fig. 22.2
1. Technique: Autoradiography
3
H = tritium, hydrogen atom
with 2 extra neutrons; it
undergoes radioactive
decay
3
H -thymidine (a nucleotide
that is one component of
the genetic material, DNA)
is used to study cell
“birthdays” (i.e. date of final
cell division)
3
H-proline, an amino acid
that is one component of
proteins, is used to trace
neuronal pathways.
 Analysis of cell birthdays
Label monkey fetus with 3H-thymidine at E33 or E56
Wait until animal matures, then perform autoradiography
Pia

Exposed to label at E56

Exposed to label at E33

Conclusion:
Postmitotic neurons
migrate towards the
pia, migrating past
neurons that
migrated previously.

Ventricle
 Technical question:
When a monkey fetus is exposed to 3H-thymidine at
embryonic day 33, shouldn’t all dividing cells take up the
label, including cells whose progeny will be dividing later,
e.g. at day 56? In that case, why is there only a narrow
band of label in the animals exposed at day 33 – why
doesn’t it extend all the way up to the pia?

Exposed Exposed
at E33 at E56
 Features of mammalian cortical development

• Dividing neuroblasts proliferate in the ventricular zone

• At some point (before birth in mammals) cells stop
dividing – i.e. they have their “birthday,” except for a
very few neuronal stem cells
• They immediately migrate towards the marginal zone,
following radial glial cells
• The order of migration is “inside out,” i.e. newly born
neurons migrate past previously migrated ones to a
point nearer the pia
• Large neurons are born earlier than small neurons
• Glial cells retain the capability of dividing throughout
the life of the animal
 Neurons and the “cell cycle”

• Are neurons able to divide, or are they “post-mitotic?”

• (Mitosis = cell division; post-mitotic = can no longer
divide)
• Look for “mitotic figures” in slices of brain tissue
• But, there’s a problem…
• Modern methods
– Autoradiography
– Bromodeoxyuridine (BRDU)

Like DNA

Fluorescent
 2. BRDU + specific neuron label

Green=BRDU
Red=neuron-specific stain
Neuronal differentiation: Control of gene
expression
membrane
membrane

nucleus
nucleus

cytoplasm
cytoplasm
 membrane

nucleus

cytoplasm
 Introduction to cell death

• 2 – 3 times overproduction of cells during

development
• Occurs in many parts of the body
• Two distinct kinds:
– Programmed (apoptotic, “suicide”)
– Necrotic (“murder”)
• In invertebrates, specific identified cell always
dies at a particular time
• Cell death program can be activated in adults,
e.g. neurodegenerative diseases