Neurogenesis Connectivity and Cell Death Flashcards
In the neuronal proliferation, what surface do ventricular zone cells extend a process towards?
The pial surface
What happens to the neuronal nuclei as they move towards the pial surface in neuronal proliferation?
The DNA is copied
What are steps 3 and 4 of the cell proliferation/cleavage process?
- The cells move back to the ventricular surface
- Cell retracts arm from pial surface
What are the two types of neuron cleavage?
Horizontal division (vertical cleavage)
Vertical division (horizontal cleavage)
What other classifications of division comes from the different cleavage types?
Vertical cleavage = symmetric division
Horizontal cleavage = Asymmetric division (differentiation)
What type of cleavage would be responsible for rapid growth of neuronal cell population?
Vertical cleavage/horizontal division
How does a cell decide on the type of cleavage?
The transcription factor
What is the notch and numb?
They are the differing transcription factors on the top/bottom of a proliferating neuronal stem cell
How can we describe the daughter cells of horizontal and vertical division in terms of notch/numb?
Vertical cleavage/ horizontal division = both cells contain notch/numb
Horizontal cleavage/vertical division = one cell contains notch(differentiates) and the other contains numb (will eventually develop notch again)
What are the two transcriptions factors that determine the fate of the daughter cells and on which sides of the cell are they located?
Notch one = pial-facing surface
Numb = ventricular surface
In terms of notch and numb, when will a cell stop its division?
Notch by itself will stop dividing
What is the mechanism of microcephaly genes?
They tilt the mitotic spindle more horizontally, meaning more vertical division, meaning less premitotic cells
What kinds of division lead to exponential vs liner growth?
Horizontal division = exponential growth
Vertical division = linear growth
What are the 5 layers of the cortex in terms of neuronal development?
Marginal zone
Cortical plate
Intermediate zone
Subventricular zone
Ventricular zone
What kinds of cells are found in the ventricular zone?
Radial glial cells
What is the order of cortical plate development and neuronal layers in the cortex?
Earliest to latest:
Cortical subplate
Cortical plate
Layer 6
Layer 5
-
-
Layer 1
What is the outer layer of the cortex?
Layer 1
What are the factors that determine the fate of a differentiating cell?
- Cleavage plane
- The location of the cell in the ventricular zone
- Migration pattern
- Age of cell at time of division
Name the types of cells differentiated by location of origin in ventricle wall from the most ventral to the most dorsal
Oligodendrocyte
GABAergic interneurons
Pyramidal neurons/cortical astrocytes
What can we say about the nature of neuronal cell migration in the developing neocortex?
Ventral cells can migrate dorsally, and the dorsal cells are in the proliferative zone and are already situated in the right spot
From ventral to dorsal, name the types of NTergic progenitor zones generated in the ventricular wall
AcH, GABA, Glu
What are the excitatory/inhibitory properties of the NTs generated in the ventricular wall?
Glu and Ach = excitatory
GABA = inhibitory
How can we describe the geometrical migration of GABAergic and Glutamatergic neurons
GABAergic migrates tangentially
Glutamatergic migrates radially
Where do GABAergic and glutamatergic neurons originate?
GABAergic = lateral and media ganglionic eminences
Glutamatergic = pallium/ cortical ventricular zone
What are the three stages of the development of glial cells in mice and around how many days into pregnancy does this occur?
- Expansion phase (symmetric division) 8 days
- Neurogenesis (asymmetric division)13 days
- Gliogenesis (asymmetric division) 18 days
What is gliogenesis?
The creation of glial cells from stem cells arise from progenitor cells
What molecule is an example of diffusible molecules responsible for the direction and characteristics of neurons/ dendrites in the marginal zone?
Semaphorin 3A
What is spatiotemporal pattern of gene expression?
it is a reference to the fact that cells differentiate at different places at different times and this affects their outcome
What two transcription factors are relevant to the specification and regionalization of mice cerebral corticies?
Emx2 and Pax 6
What areas of the brain were impacted by deficiencies in transcription factors?
Deficiency in Emx2 led to smaller visual cortex (larger motor to compensate) and a deficiency in pax6 led to a smaller motor cortex/ somatosensory cortex (larger visual cortex to compensate)
What are the three phases of pathway formation?
- Pathway
- Target
- Address
What is the necessary environmental component for the extension of neurons, and what molecules are attached to this that are important?
The extracellular matrix allows for the growth of neurons because they hold the laminin molecules
Why are laminin molecules important for axon growth?
They bind to the integrin molecules of the axon to direct the growth
What parts of the growth cone search for clues in the ECM?
Filopodia and lamellipodia
What is the role of a microtubule in the growth cone?
They are constantly assembled down the axon and are responsible for cell shape
What are the roles of actin molecules in the growth cone?
They are the growing part of the cone and interact with myosin motor proteins to grow before the microtubules take their place and are eventually left behind
What is the role of a CAS?
A cell adhesion molecule holds axons together, as they typically grow together and move as a group
What is the main challenge in wiring the brain?
The distances between connected structures
What is the role of a pioneer axon?
It stretches as the nervous system expands, it then guides the growth of neighboring axons (connecting dots)
What is a pioneer tract?
It is the first group of axons to grow and find targets, they form a trail for other axons to follow.
What are the two molecularly provided guidance clues to neuronal growth?
Chemoattraction and chemorepulsion
What is the target area of growth for a pioneer tract called?
The target trophic support
What causes the decussation of neurons in terms of guidance clues when there is a high concentration of chemoattractants and chemorepellents in the midline?
When the axons are on the initial side, they express receptors to the chemoattractants, and after they grow across the midline, they express the chemorepellent receptor and grow away form the midline
How did the conclusion come about that growing axons have chemical markers that are matched by complementary chemical markers?
There are too many neurons to individually code the pathfinding for each neuron
How did Roger Sperry study the topographic axon map of eyes?
He cut and rotated frog eyes, and they saw the world upside down
What information did the frog eye experiment give us?
Optic nerves from the retina connected to the same place in the tectum
What is the role of ephrin in the growth of retinal nerves?
Ephrin A2 and A5 are responsible for the topographic arrangement of retinal cone growth. Retinal cones have ephrin A3 receptors. When ephrin A2 was applied globally, nerves died indicating that ephrin A2 is a growth repellant.
What parts of the tectum do the retinal tracts attach to?
Temporal retina attach to anterior tectum
Nasal retina attach to posterior tectum (or both)
What are the three steps to CNS synapse formation?
- Filipodium contacts axon
- Synaptic vesicles and active zone proteins are recruited to the presynaptic membrane
- Receptors accumulate on postsynaptic membrane
What is the difference between necrosis and apoptosis?
Necrosis is accidental cell death (swelling/rupture) and apoptosis is programmed cell death (shrinkage/fragmentation)
At what age does neural pruning in the embryo end?
25 weeks
What determines neuronal survival?
Competition (for trophic factors)
What are the types of trophic factors + mechanisms?
Endocrine - from the blood/circulation
Paracrine - from other cells
autocrine/juxtracrine - from the cell itself
