Embryology II

Question 1

Three areas of secondary neurogenesis

Answer 1

1) External Granular Layer 2) Subventricular Zone 3) Dentate Gyrus

Question 2

What occurs in the External Granular Layer?

Answer 2

Post-natal neurogenesis. Granule neurons arise here and migrate into the cerebellum. Neurons initially located near the fourth ventricle migrate BEFORE they are “post-mitotic” and form a secondary zone of neurogenesis (EGL). This can continue for up to two years.

Question 3

What occurs in the Subventricular zone?

Answer 3

Post-natal neurogenesis. Olfactory bulb neurons arise here and migrate to the olfactory bulb along the rostral stream. Neurons originally located near the anterior wall of the lateral ventricles migrate BEFORE they are post mitotic and form this secondary zone of neurogenesis.

Question 4

What occurs in the Dentate Gyrus?

Answer 4

Post-natal neurogenesis. Neurons of the hippocampus arise here and migrate into the hippocampus. Neurons originally located in a ventricular zone migrate here BEFORE they are post-mitotic and form this secondary zone of neurogenesis.

Question 5

What is the pre-plate?

Answer 5

In the cortex, the first cells to become post-mitotic migrate several cell lengths from the VZ and form a new zone known as the pre-plate. The pre-plate is the precursor of the marginal zone, intermediate zone, and sub-plate.

Question 6

What is the sub-plate?

Answer 6

The sub-plate is formed from some of the earliest cells in the pre-plate and play “pioneering” roles in circuit formation. Most of these cells die out once their pioneering roles are finished, and they are considered a transient population.

Question 7

What is the role of radial glia in neuronal migration?

Answer 7

Radial glia are cells that extend from the ventricle to the surface. Neurons appear to use these cells as guides during migration, and radial glia may play a role in arranging cells that serve similar functions into columns. Radial glia thus serve as a scaffold for migrating cells in the “inside-out” cortical development.

Question 8

What are the three stages of neuronal migration in cerebral development?

Answer 8

1) Onset of migration 2) Ongoing migration 3) Stopping migration.

Question 9

What genes play roles in the onset of migration?

Answer 9

The filaminA gene (FLNA) encodes an actin-binding crosslinking gene that assists with the onset of migration. Mutations in this gene lead to periventricular heterotropia (PH).

Question 10

What genes play a role in ongoing migration?

Answer 10

The LIS1 and doublecortex (DCX) genes play a role in continuing migration of neurons. LIS1 mutations cause a lack of layer specificity in the cortex and lead to Type I lissencephaly (smooth brain). DCX mutations cause development of a band of heterotrophic neurons midway between the ventricles and the cortex, hence “double cortex” syndrome.

Question 11

What genes play a role in stopping migration?

Answer 11

The reeler, Dab1, Vldlr, and Apoer2 genes play roles in stopping migration. Mutations in reeler cause premature stoppage of migration at the pre-plate and an “inside-out” brain development.

Question 12

What is radial migration and what class of neurons undergoes radial migration?

Answer 12

Radial migration is the movement of neurons perpendicularly away from the ventricles to the cortex along radial glia. In general, glutamate containing neurons, AKA pyramidal cells, use radial migration to get to their characteristic positions.

Question 13

What is tangential migration and what class of neurons undergoes tangential migration?

Answer 13

Tangential migration is the movement of cells away from the ventricular zone at a non-perpendicular angle. Typically these are GABA containing, inhibitory neurons.

Question 14

What is chain migration and what class of neurons undergoes chain migration?

Answer 14

Chain migration is the movement of cells away from the subventricular zone in a line or chain. Neuronal precursors move as chains in a pathway known as the rostral migratory stream.

Question 15

What are neural crest cells?

Answer 15

Neural crest cells are the cells between the neuroectoderm and epidermis during the neural plate stage. After the neural crest closes, they constitute the mass of cells on top of the dorsal tube.

Question 16

What neuronal populations do the neural crest cells give rise to?

Answer 16

Neural crest cells give rise to the peripheral nervous system as well as other cell types like pigment cells and cartilage. Their derivatives are found in diverse locations including the gut, skin, and sensory ganglia.

Question 17

What influences the differentiation of neural crest cells?

Answer 17

A neural crest cell’s location along the rostral-caudal axis heavily influences its eventual fate. Also, the specific environments they encounter as the migrate may also influence their pattern of differentiation.

Question 18

How do neural crest cells migrate?

Answer 18

Neural crest cells do not follow glia guides. They interact with proteins on other cell surfaces and in the ECM to guide their movement, including laminin and fibronectin, and connect via integrins. They are also repelled by inhibitory signals on non-permissive surfaces.

Question 19

When does cell death occur in the nervous system?

Answer 19

Large amounts of apoptotic cell death are involved in pattern formation, brain morphogenesis, removal of unnecessary neurons, and matching neuronal populations to target fields. In the hindbrain, cell death plays a role in defining the identity of each segment.

Question 20

What are neurotrophins?

Answer 20

Neurotrophins are a class of molecules that neurons receive when they initially establish contact with target organs or from pre-synaptic (input) cells and glia. They serve as important regulators of neuronal survival, development and function, and appear to serve as inhibitors of apoptosis.

Question 21

What is synapse elimination and how and where does it occur?

Answer 21

Initially, many neurons may innervate the same muscle cell. The neuron with the strongest connection (able to induce an AP in the muscle) receives the neurotropins, and the others eventually withdraw their synapses leaving only one neuron to the muscle cell. Does not involve neuron death, the other neurons innervate other muscle cells. This occurs in NMJs and the CNS.

Question 22

How do axons extend to find their targets?

Answer 22

The tip of the axon, the growth cone, sends fine processes, filopodia, ahead to sense the environment and provide direction for the neuron to extend, stop, retract, or turn.

Question 23

Name one attractive long range and six short range axonal guidance molecules.

Answer 23

Long range: netrins. Short range: (cell surface) cadherins, CAMs; (ECM) collagen, laminin, fibronectin, proteoglycans

Question 24

Name two repulsive long range and three repulsive short range axonal guidance molecules.

Answer 24

Long range: semaphorins, netrins. Short range: (cell surface) semaphorins, ephrins; (ECM) tenascin.

Question 25

What are the three factors that affect the ability of neurons to regenerate?

Answer 25

1) The ability of axons to grow. 2) The presence of molecules that promote growth. 3) The presence of molecules and receptors that inhibit growth.

Question 26

Do CNS axons have the ability to regenerate?

Answer 26

No. If a peripheral nerve is implanted at the site of injury the CNS axons can then grow several centimeters.

Question 27

What molecules promote axonal growth?

Answer 27

Schwann cells may produce NGF or other trophic factors that aid in growth. Also, Fibroblast Growth Factor (FGF) also aids in axonal growth, as do neurotrophins.

Question 28

What molecules and receptors inhibit axonal growth?

Answer 28

CNS myelin expresses a protein, Nogo, that interacts with the Nogo-66 receptor and inhibits axonal growth.

Question 29

What are the normal post-natal changes in brain morphology?

Answer 29

At birth, the density of neural connections is low. During the first year there are dramatic changes in the size of the soma and number of interconnections of neurons. The number of dendrites greatly increases.

Question 30

How does Autism Spectrum Disorder affect normal developmental changes in neuronal morphology?

Answer 30

The brains of ASD patients show abnormally high increases in size, esp in white matter areas. Also, neuronal cell bodies are often smaller and dendrites branch less.

Question 31

How does Down Syndrome affect normal developmental changes in neuronal morphology?

Answer 31

In normal development, the density of cortical dendritic spines increases as they thicken. Individuals with Down syndrome have abnormally thin and short dendritic spines.

Question 32

When does myelination begin in the periphery, spinal cord, and brain?

Answer 32

Myelination first begins during embryonic stages in the periphery. Then in the spinal cord during the first trimester, and is present in the brain by the third trimester.

Question 33

When does myelination of the cortical tracts, and corticospinal tract begin?

Answer 33

Myelination of several cortical tracts begins after birth. Myelination of the corticospinal tract, however, begins before birth but only to the medulla. Myelination of the tract caudal to the medulla does not occur until after birth.

Question 34

Describe two ways in which the function of GABA receptors is developmentally regulated.

Answer 34

1) Different isoforms of the GABA receptor are expressed in embryonic stages than in the adult. 2) GABAr is a Cl- channel, and ECl during developmental stages is less negative due to increased intracellular [Cl-] (don’t ask how this makes sense) that result from lower expression of KCC2 Cl- extruder but normal NKCC accumulator transporters.