Download for neural fate

Neural Development
• How does a single cell make a brain???
• How are different brain regions specified???
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Neural Development
• How do nerve become nerve cells?
– Environmental factors
• Inductive events
• Positional cues
– Genetic factors
• Competence
Cell lineage
Timing
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Neural Development depends on genes and environment
Keywords in Development
Induction: Cells are instructed to adopt a fate by signals in the environment
Competence: the ability of a cell to respond to a signal. It depends on the
receptors, transcription factors, etc expressed by the cell
Determination: A cell is restricted in its developmental potential.
Differentiation: Cell elaborates a specific developmental program.
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Complexity of the human brain
100,000,000,000 neurons
Each neuron makes 1000 synapses
Regional specializations
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Major Processes in Development
egg
1n + 1n
zygote
=
2n
1. Mitosis
-cell division
2. Patterning
-cells are arranged in proper positions
-the body plan is established
3. Differentiation
-cells become different from each other
-they acquire specific functions
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Initial Steps in the Development of the Nervous System:
Fertilization
Cleavage
Gastrulation
Neurulation
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Looking at early development of the nervous system: Xenopus Frog
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Early events in neural development
Gastrulation :
Gastrulation is the process by which the embryo acquires 3 germ
layers. There is intense cell movement and rearrangement
Ectoderm Major tissues of the Nervous System, Epidermis
Mesoderm Connective Tissue, Muscle, Vessels
Endoderm  guts, lungs, liver
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movie
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Early events in neural development
Gastrulation
Neurulation
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Neurulation: Formation of the Neural Tube
After Gastrulation comes Neurulation.
During Neurulation, the neural plate invaginates, and the neural folds close
to form the neural tube.
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Long After Neurulation:
Neural Crest
Neural Tube
Rostral
Brain
Caudal
Spinal Cord
PNS (sensory
ganglia, ANS),
melanocytes,
adrenal medula
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- How do ectodermal cells become neural cells?
- How is polarity established?
Dorsal Ventral
?
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Early events in neural development
Gastrulation
Neurulation
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Classic experiment showing the induction of the
nervous system
Hans Spemann discovered the
organizer----Nobel 1935
Expt: Transplant different parts of the
developing embryo (donor)
into another embryo (host)
Result: 1) If the dorsal lip is transplanted,
a second embryonic axis forms
2) The second embryo has
both host and donor tissue
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The organizer region is responsible for converting
ectoderm into neural cells
Model: Inductive signal in dorsal lip instructs ectoderm
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The organizer region is responsible for converting
ectoderm into neural cells
early
late
MODEL: Organizer has instructed cells to become neural
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How does the organizer instruct epidermal cells?
Experiment 1: Neurons can form in the absence of the organizer
The default is to become neural
Model: Epidermis makes local signal that inhibits neural fate
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How does the organizer instruct epidermal cells?
Experiment 2:
Inject blastula with genes of interest. Do any cause animal cap to
become neural?
Result:
Expression of a dominant negative mutant
of a BMP receptor results in neural fate.
Model: BMP signal instructs cells not to become neural
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Activation of BMP signaling inhibits the neural fate
NOT NEURAL
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How does the organizer instruct epidermal cells?
Experiment 3:
Same idea as 2: Inject blastocyst with genes from the organizer and see if any
cause the animal cap to become neural
Neural fate
(?)
Take the animal
cap
Inject mRNAs
Noggin is a secreted protein, expressed in the organizer and later in the
notocord.
Noggin inhibits BMP signaling.
Follistatin and chordin have similar functions.
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Inhibition of BMP signaling makes cells adopt neural fate
== NOGGIN
NEURAL
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Current Model for how cells become neural
1) Default state is neural
2) Local secretion of BMPs by epidermis inhibits neural fate
3) Local secretion of noggin, chordin by dorsal lip or mesoderm
inhibits BMP signaling
4) Inhibition of BMP signaling give rise to neural fate
Double Inhibition Model for Neural fate
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Model: The ‘double inhibition model’ for neural fate
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A cell’s fate will depend on the signals to which it is
exposed as well as the developmental history of the
cell (which genes they express)
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