Neural Development Flashcards
What 4 steps outline vertebrate neural tube formation?
- Shaping and initial folding
- Elevation (of sides)
- Convergence (of sides)
- Closure and separation of neural tube from epidermis
How do the cells of the neural plate change during folding?
The mediolateral edge shrinks, turning the cells wedge-shaped.
What pathway mediates the folding of the neural plate and the change in shape of the neural plate cells?
The Planar Cell Polarity (PCP) signalling pathway.
What 2 functions does the Planar Cell Polarity signalling pathway drive?
- Convergent extension
2. Apical constriction
How is the Planar Cell Polarity signalling pathway activated?
By non-canonical Wnt signalling.
In the Planar Cell Polarity signalling pathway, how are cadherins interactions at adherens junctions maintained?
By the action of Celsr1 at the apical membrane.
In the Planar Cell Polarity signalling pathway, how is actino-myosin contraction mediated?
By the action of PDZ-RhoGEF (downstream of Wnt).
What do we call the cells that are left over between the neural tube and the epidermis immediately after neural tube formation?
Neural crest cells.
What is spina bifida?
A human defect arising from the failure of neural tube closure.
What genes are involved in spina bifida? How can the expression of this gene be altered?
Alx1, Pax3, Alx3. Needs folic acid for expression. If mother doesn’t get enough folic acid during pregnancy then spina bifida can occur.
Why does lack of folic acid during pregnancy put a child at risk of spina bifida?
Folic acid activates lipoprotein receptor SR-BI which activates Alx1, Pax3, Alx3.
What do vertebrates have during development that other chordates don’t have?
The neural crest!
What gene has been shown to be critical for neural crest differentiation?
FoxD3.
What is sometimes referred to as “the 4th germ layer”?
The neural crest!
What tissues do neural crest cells give rise to?
PNS, endocrine structures, pigment cells, facial cartilage/bone, connective tissue.
Are neural crest cells multipotent? How was this determined?
Yes, through fate-mapping experiments.
What mechanism specifies the fate of neural crest cells in different areas of the body?
Local paracrine signalling cues and regulatory transcription factors.
In addition to mesoderm, neural crest cells can also give rise to ____. What kinds of cells are these?
Bone. As osteoblasts and eventually osteocytes.
What can result from neural crest defects?
Truncated or totally absent structural tissues (ex: missing clavicles, etc.)
What did Julia Platt show regarding neural crest cells?
That they can also produce bone (at the time, dogma was that only mesoderm became bone).
What is DiGeorge syndrome?
A disease resulting in a connection between the aorta and pulmonary artery (aortopulmonary window).
What causes DiGeorge syndrome? What TF is missing?
The neural crest cells that are supposed to differentiate into cardiac tissue fail to migrate to the heart and form a septa. Lacking Tbx1.
Cells in Ciona intestinalis have similarities to neural crest cells. What are they missing?
Transcription factor “twist”, which can cause them to exhibit the same migration as neural crest cells.
What patterns the AP axis (with neural ectoderm) in Xenopus?
A Wnt morphogen gradient. + Hox genes
How is DV polarity established in the neural tube?
Sonic hedgehog (Shh) secretions from the notochord (ventral) and BMP4/Wnt secretion from the ectoderm (dorsal).
What are the 5 TF subsections established by the Shh morphogen gradient in the neural tube? (dorsal to ventral)
- Pax7
- Pax7+Pax6
- Pax6
- Pax6+Nkx6.1
- Nkx6.1
What are the 3 components of Axon Guidance?
- Pathway selection
- Target selection
- Address selection
Describe the “pathway selection” component of Axon Guidance.
Developing neuron (axon) must find a way to get to the target cell.
Describe the “target selection” component of Axon Guidance.
Developing neuron (axon) must form synapses with the appropriate target cell.
Describe the “address selection” component of Axon Guidance.
Developing neuron (axon) must prune synapses to remove sub-optimal connections.
How is growth of the growth cone at the end of the growing axon regulated?
Extracellular matrix glycoproteins signal Rho GTPases to make adjustments to the actin/microtubule cytoskeleton.
According to Rita Levi-Montalcini’s experiments, what happens to the growing peripheral neurons when you cut off the limb bud they’re trying to grow into?
The developing peripheral neurons die.
What is the function of nerve growth factor (NGF)(neutrophins)?
Promote axon outgrowth, survival, and differentiation.
What 4 molecules are responsible for guiding the growing axon?
- Ephrins
- Netrins
- Slit
- Semaphorins
What general mechanism can describe the action of axonal guidance molecules?
Some give off repulsive signals on one side of the axon while others on the opposite side give off attractive signals, turning the axon.
What is present in the spinal cord that prevents mechano and pain/temp neurons from projecting ventrally?
Semaphorin 3 is present in the ventral region of the spinal cord.
How did researchers originally figure out the somatosensory cortical map?
By shocking specific parts of a conscious patients brain and noting where they felt it.
How are sensory maps generated in the retina?
Ganglion cells are guided by an ephrin gradient in both axes coupled with Eph-EphR repulsion (low nasal EphR, high lateral EphR).
