Lecture 9 Flashcards
the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube; the formation of the nervous system from the ectoderm
neurulation
In neurulation, the embryo is called the ___.
neurula
when the anterior part of the neural tube forms a series of bulges called vesicles, which become the primary anatomical regions of the brain: the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon)
regionalization
What are the 4 regions formed in regionalization?
forebrain, midbrain, hindbrain, spinal column
the growth and development of nervous tissue
neurogenesis
What are the steps in neural development?
neurulation, regionalization neurogenesis migration differentiation axon guidance synapse formation cell death synaptic rearrangement
What are the 3 primary germ layers during gastrulation?
ectoderm
mesoderm
endoderm
a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a multilayered structure known as the gastrula
gastrulation
The ectoderm forms what?
epidermis
CNS
PNS
The mesoderm forms what?
kidneys reproductive organs bones muscles vascular system
The endoderm forms what?
intestines
lungs
liver
____ cells are pre- programmed to become neurons
ectodermal
What does dissociation from other cells cause ectodermal cells to do?
differentiate into neurons
What causes ectodermal cells to differentiate into the skin?
inhibitory signals from other ectodermal cells (remaining intact)
How does the mesoderm affect ectoderm differentiation?
it blocks the signals from other ectoderm, allowing it to differentiate into neurons
What is the role of BMP 4?
It induces ectodermal differentiation into skin, even when dissociated
portion of mesoderm that normally gives rise to the notochord
the organizer
a cartilaginous skeletal rod supporting the body in all embryonic and some adult chordate animals
notochord
What does the neural crest form?
PNS
Where do the ectodermal placodes arise from and what do they form?
- non-neuronal ectoderm
- sensory epithelia and cranial nerves
What does the neural tube form?
brain and spinal cord
when the neural tube fails to close at the head (fatal)
anencephaly
when the neural tube fails to close at the tail (correctable)
spina bifida
a group of related genes that control the body plan of an embryo along the head-tail axis; expressed head to tail
Hox (homeobox domain)
What determines dorsal-ventral polarity?
the notochord
What happens if we remove the notochord?
no motor neurons form
What happens if we transplant the notochord?
ectopic motor neurons form
The ___ is expressed in the floor plate of the neural tube and the notochord and ___ is expressed in the roof plate of the neural tube and the ectoderm. Both signals contribute to ____.
Shh
BMP
dorsal-ventral polarity
Shh and BMP ____ to specify the identity of neural progenitors.
antagonize each other
BMP in the epidermal ectoderm leads to the formation of ____
dorsal interneurons
Shh in the notochord (mesoderm) leads to the formation of ____
motor and ventral interneurons
a signaling molecule that acts directly on cells (not through serial induction) to produce specific cellular responses dependent on morphogen concentration. During early development, morphogen gradients generate different cell types in distinct spatial order.
morphogen (french flag model)
Which signaling molecules makes use of the french flag model?
Shh
Differing Shh levels induce different combinations of ____
transcription factors
Shh signaling establishes a spatial organization of ____.
Distinct classes of neurons (motor or interneurons) arise from each ____.
progenitor cells
progenitor domain
when a single cell layer (neural tube) becomes a multi-layered structure (brain/spinal cord)
proliferation
neural precursors with limited self- renewal capabilities
progenitor cells
Progenitors cells give rise to ___ and ___ (more restricted)
radial glia
basal progenitors
How does a cell know what to become?
extrinsic influences (cell-to-cell interactions) intrinsic influences (programmed): gene profile based on developmental history
Cells of the neural tube give rise to both immature ___ and ___
neurons
glia
Sequential generation of neurons and glia depends on what two things?
- presence of growth factors at specific developmental times
- signaling pathways they activate
The neocortex consists of __ layers.
6
Layers II, III, V, and VI consist of what cells?
glutamergic pyramidal cells
Layer IV consists of what cells?
GABAergic stellate cells
Neuroblasts migrate along ___ and “exit” at the
appropriate location.
radial glia
Cortical layers form ___.
inside out
What molecules induce the formation of the following cells from a neural crest progenitor: sensory neuron, sympathetic progenitor, melanocyte, chromaffin cell progenitor
sensory neuron: leukocyte inducing factor (LIF)
sympathetic progenitor: FGF2
melanocyte: stem cell factor
chromaffin cell progenitor: glucocorticoids
What molecules induce the formation of the following cells from a sympathetic progenitor: adrenergic neuron, cholinergic neuron
adrenergic neuron: NGF
cholinergic neuron: ciliary neurotrophic factor
What molecule induces the formation of the chromaffin cell from a chromaffin cell progenitor?
glucocorticoid
What are the 3 phases of axon navigation to target?
- pathway selection: which route to take
- target selection: which structure to innervate
- address selection: which cells within target
What guides axonal growth?
physical cues (“functional molding” of random connections)
What did the experiment with a rotated eye and severed axons in a frog show?
frogs couldn’t correct; the cells and fibers of the brain and cord must carry some kind of individual identification tags, presumably cytochemical in nature, by which they are distinguished one from another
big actin-supported extension of a developing or regenerating neurite seeking its synaptic target
axon growth cone
How do axon growth cones function?
The highly dynamic nature of growth cones allows them to respond to the surrounding environment by rapidly changing direction and branching in response to various stimuli.
a long, slender, tapering pseudopodium, as found in some protozoans and in embryonic cells
filopodia
a flattened extension of a cell, by which it moves over or adheres to a surface
lamellipodia
What two molecules aid in axon guidance and cytoskeleton formation?
- filopodial protrusion by actin polymerization
- microtubules in axon shaft
Axon migration affected by ___
signals (repulsive, attractive, permissive)
What 3 signals affect axon migration?
diffusible factors - secreted by cells (slit semaphoring, NGF)
extracellular matrix molecules (laminin, collagen, fibronectin)
cell-cell contact - surface receptors/ligands (CAMs, Cadherins, ephrins)
What extracellular metric molecule do neurons prefer the most? Why?
neurons prefer laminin over collagen (in vivo); laminin binds to integrins on axons
unidirectional movement of a cell, in response to a chemical gradient of ligands; diffusible factors
chemoattraction/chemorepulsion
Cell as the midline of the brain secrete ____. Axons with ___
migrate towards midline (chemoattraction).
netrin netrin receptors (DCC)
Midline cells also secrete __. Axons that cross the midline upregulate ___. Cells with these receptors are repelled by ___ (chemorepulsion)
slit
robo (slit receptor)
slit
What is the function of slit and robs receptors?
The prevent cells that cross the midline from re-crossing
Cells with robo receptors stop responding to ___.
netrin
Describe the role of netrin and slit in retina-tectal projections.
- Netrin attracts axons to the optic chiasm
- those that express Slit cross the chiasm.
Chemorepellent responsible for retinal ganglion cell outgrowth onto tectal membrane extracts
ephrins
How does ephrin work?
similar to french flag model… uses a gradient of ephrin receptors on the retina and ephrin ligands on the tectum to match axonal growth
What are the steps in synapse formation?
- dendritic filopodium contacts an axon
- contact leads to recruitment of synaptic vesicles in presynaptic cell
- formation of active zone triggers clustering of postsynaptic receptors
Adhesion molecules (____) are expressed on both pre- and post- synaptic cells to ___.
N-cadherin
stabilize the synapse
What are the steps in synapse formation at the NMJ?
- growing motor neuron secretes agrin
- agrin interacts with MuSK receptors on muscle
- activation of MuSK leads to clustering of ACh receptors via rapsyn
- basal lamina stimulates Ca2+ entry and NT accumulation
- both membranes undergo cytoskeletal changes
- Synaptic transmission occurs rapidly; final maturation takes weeks
How does a growth cone know which of the 30 muscles to innervate?
splicing for synapse specificity mediates self-avoidence
