Transcript development i: proliferation, migration

AMHERST COLLEGE
INTRODUCTION TO NEUROSCIENCE
MONDAY, FEBRUARY 4, 2008
DEVELOPMENT I: PROLIFERATION, MIGRATION
• Today’s reading:
Chap. 7(178-195);
23(690-698)
• Wednesday:
Chapter 23 (698708)
Neuroanatomy questions
1.
2.
3.
What is an exception to the rule that “ganglia”
are in the PNS?
Place in rostro-caudal order:
•
Inferior colliculus
•
Thalamus
•
Medullary respiratory center
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)
Course Outline and Readings
Date
OutlineTopic
of development
Reading
Introduction
January 28
30
February 1
Introduction to neuroscience
Chapter 1
SG Approaches to studying brain and
behavior
Chapter 2
ST Outline of neuroanatomy
Chapter 7 (168-180; 193-199;
205-235); Chapter 15 (490-497)
Development of the nervous system
4
SG Neurogenesis, migration
6
Axon pathfinding; cell death
8
Role of neural activity in development
Chap. 7 (178-195); 23 (690-8)
Chapter 23 (698-708)
Sheetz AJ, Williams RW, and Dubin MW Severity of ganglion cell death during early
postnatal development is modulated by both neuronal activity and binocular competition.
Visual Neuroscience 12 (1995) 605-610.
Electrical signalling
11
Membranes and membrane potentials
Chapter 3
13
Action potential
Chapter 4
Proliferation
Fertilized egg
(single cell)
Whole organism
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’
→
Fig. 7.9, 7.10, 7.13
Basal
ganglia
Line of Thalamus
“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
3H
= tritium, hydrogen atom
with 2 extra neutrons; it
undergoes radioactive
decay
3H
-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)
3H-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
Exposed to label at E56
Exposed to label at E33
Pia
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
at E33
Exposed
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