Lecture 8 - Structures and Development of the Nervous System + Lecture 9 - Patterning of the Nervous System Flashcards

1
Q

Human embryo formation: ~day 0-5.

  • The first days there is continuing process called … (= rapid cell division).
  • The … is formed by day 4 and has the same size as the zygote, because the zona … is still intact.
  • Blastulation: the cells, called …, secrete fluid and the outermost cells become tightly … together in the process of compaction.
  • …/blastula is formed by day 5. Two layers are formed: the ….. (or embryoblast) forms the embryo and is the source of … embryonic stem cells. The outer layer, called …, later forms the placenta. Note polarity (embryonic pole).
  • The fluid inside the blastocyst is called the … . Around the time the blastocyst is formed, the zona pellucida … .
A

Human embryo formation: ~day 0-5.

  • The first days there is continuing process called cleavage (= rapid cell division).
  • The morula is formed by day 4 and has the same size as the zygote, because the zona pellucida is still intact.
  • Blastulation: the cells, called blastomeres, secrete fluid and the outermost cells become tightly bound together in the process of compaction.
  • Blastocyst/blastula is formed by day 5. Two layers are formed: the inner cell mass (or embryoblast) forms the embryo and is the source of pluripotent embryonic stem cells. The outer layer, called trophoblast, later forms the placenta. Note polarity (embryonic pole).
  • The fluid inside the blastocyst is called the blastocoel. Around the time the blastocyst is formed, the zona pellucida dissapears.
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2
Q

Human embryo formation: ~week 2-3

  • During the 2nd week the inner cell mass differentiates into two layers, called the …, which consists out of epiblast and … . This disc is a flat slice across the developing sphere.
  • The hypoblast facing the blastocoel becomes the …. and above the epiblast becomes the … cavity.
  • Gastrulation: in week 3 the two primary germ layers become three germ layers: …, mesoderm and … . The cell mass is now known as gastrula.
  • The first step of gastrulation is the formation of the …: it cuts in the epiblast layer from caudal end (anus) in toward the end that will eventually become the head (the rostral end).
  • The second step of gastrulation is the … of epiblast cells: they are moving … so they end up between the original epiblast layer and the hypoblast. The first layer to invaginate ends up closest to the hypoblast: … . Then, the second layer will be the …, and the epiblasts will become the ectoderm.
A

Human embryo formation: ~week 2-3

  • During the 2nd week the inner cell mass differentiates into two layers, called the bilaminar disc, which consists out of epiblast and hypoblast. This disc is a flat slice across the developing sphere.
  • The hypoblast facing the blastocoel becomes the yolk sac and above the epiblast becomes the amniotic cavity.
  • Gastrulation: in week 3 the two primary germ layers become three germ layers: ectoderm, mesoderm and endoderm. The cell mass is now known as gastrula.
  • The first step of gastrulation is the formation of the primitive streak: it cuts in the epiblast layer from caudal end (anus) in toward the end that will eventually become the head (the rostral end).
  • The second step of gastrulation is the movement of epiblast cells: they are moving down so they end up between the original epiblast layer and the hypoblast. The first layer to invaginate ends up closest to the hypoblast: endoderm. Then, the second layer will be the mesoderm, and the epiblasts will become the ectoderm.
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3
Q

How does gastrulation create the antero-posterior body axis?

Name a few structures that each of the three germ layers will form.

A

Primitive streak (formed in first step of gastrulation) determines the midline of the body, and separates the left and right sides.

  • Ectoderm: will form skin, whole nervous system, hair, sinuses, mouth, anus, nose, etc.
  • Mesoderm: will form muscles, bones, spleen, kidneys, heart, lungs, reproductive system, etc.
  • Endoderm: will form linings of lungs, tongue, digestive tract, urethra and associated glands, etc.
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4
Q

What does the appearance of Koller’s sickle indicate?

What is the role of Hensen’s node?

A

In the chick embryo the appearance of Koller’s sickle is the first sign that gastrulation is underway.

Hensen’s node is the ‘organiser’ for the process of infolding during gastrulation. The order in which the cells enter the blastocoel through Hensen’s node determines their specification in the embryo.

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5
Q

How are the ‘organisers’ for gastrulation called for different species:

  • Birds
  • Amphibians
  • Mammals
A
  • Birds = Henson’s node
  • Amphibians = Spemman’s organiser
  • Mammals = primitive knot (or node)
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6
Q

Human embryo formation: ~ week 4

  • First step of … is creation of notochord. The notochord causes the cells above it to form a thick flat plate of cells, called the … .
  • The neural plate then …. on itself and seals itself into a tube known as the … that fits underneath the ectoderm.
  • The borders of where the neural plate had been pulled under with become the neural … . The neural tube will become the brain and spinal cord.
A

Human embryo formation: ~ week 4

  • First step of neurulation is creation of notochord. The notochord causes the cells above it to form a thick flat plate of cells, called the neural plate.
  • The neural plate then bends back on itself and seals itself into a tube known as the neural tube that fits underneath the ectoderm.
  • The borders of where the neural plate had been get pulled under with it, and become the neural crest. The neural tube will become the brain and spinal cord.
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7
Q

The neural crest is sometimes called the fourth germ layer, because these cell will form structures as well. Which structures?

A
  • Sympathetic and parasympathetic nervous systems
  • Melanocytes
  • Schwann cells
  • Dorsal root ganglia
  • Some bones and connective tissue of the fase.
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8
Q

What results did we get out of the Spermann & Mangold experiments of ‘The role of the organizer in embryonic development’?

A

The vital role of the organizer in embryogenesis was confirmed via transplantation experiments. Once they transplanted the organizer part of the embryo, it started to mis-form.

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9
Q

The molecular basis of the organizer is described in the role of B-catenin.

What do Wnt/B-catenin, siamois and twin, ventral and dorsal pole have in common?

A
  1. Wnt/B-catenin activates siamois and twin gene, which lead to transcription of siamois and twin proteins.
  2. Siamois and twin induce synthesis of organizer proteins.
  3. At ventral pole of embryo B-catenin is degraded and at dorsal pole it is stabilized. This is where Spemman’s organizer arises from.
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10
Q

How does Wnt signalling pathway influence B-catenin degradation and thus, neural development?/Describe this signalling pathway.

A
  1. The Wnt signalling pathway passes signals from cell surface receptors (e.g. Frizzled) to control DNA expression in the nucleus.
  2. Stimulation by Wnt causes release of Dsh (Dishevelled), which inhibits the axin/GSK-3/APC‘destruction complex’, that normally promotes degradation of B-catenin.
  3. B-catenin can now enter the nucleus and form another complex that binds to DNA and turns on expression of siamois and twin genes.
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11
Q

The neural inducer molecules (noggin, chordin and follistatin) from the notochord cause neural induction. How does this mechanism work and what role has BMP4 in this?

A
  • The action of BMP4 (bone morphogenic protein 4) induces ectodermal cultures to differentiate into epidermis, so it inhibits differentiation into neural cells.
  • During neural induction noggin, chordin and follistatin are produced by the notochord and inhibit the activity of BMP4.
  • This causes ectodermal cells above the notochord to differentiate into neural cells.
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12
Q

Fusion of neural plate requires regulation of cell adhesion molecule expression. The neural plate switches from E-cadherin (presumptive epidermis) to N-cadherin (neural plate) and N-CAM expression.

What is the (good) consequence of this?

A

The epidermis and neural tissues can now recognize each other as being the same, and this stops binding of neural tissue to epidermis.

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13
Q

Cells of neural crest show plasticity:

  • They can give rise to either … or parasympathetic neurons depending on their …. position. In this case, differentiation depends on … cues.
  • Anterior part gives rise to … neurons (acetylcholine). Posterior part gives rise to … neurons (noradrenaline).
A

Cells of neural crest show plasticity:

  • They can give rise to either sympathetic or parasympathetic neurons depending on their anterior-posterior position. In this case, differentiation depends on positional cues.
  • Anterior part gives rise to parasympathetic neurons (acetylcholine). Posterior part gives rise to sympathetic neurons (noradrenaline).
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14
Q

Neural tube stem cell proliferation gives rise to all CNS nerve cells, astrocytes and oligodendrocytes.

Where does replication occur? What kind of migration happens during replication?

A

Replication occurs in the ventricular zone of the neural tube (close to lumen).

During replication the stem cells migrate through the neural tissue: daughter cells can remain to generate more progeny cells or they can migrate out to form neurons or glial cells.

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15
Q

Formation of radial glial cells: under the influence of genes (e.g. …, HX2, … and EMX2), neural stem cells produce radial glia, which extend a process from the ventricle surface to the … surface.

Anterior Posterior polarity of the neural tube: the formation of the neural tube does not occur all at one along its full length. It begins in the … at embryonic day 20 and then continues towards each … . Openings left at each end are called the anterior (cranial) and posterior (caudal) … . Anterior neuropore closes on day … and posterior neuropore on day … .

Dorsal view of human neural groove: … are balls of mesoderm that mature into the segmented … skeleton. Each pair is added … from head to tail down the length of embryo.

A

Formation of radial glial cells: under the influence of genes (e.g. FOXG1, HX2, PAX6 and EMX2), neural stem cells produce radial glia, which extend a process from the ventricle surface to the pial surface.

Anterior Posterior polarity of the neural tube: the formation of the neural tube does not occur all at one along its full length. It begins in the middle at embryonic day 20 and then continues towards each end. Openings left at each end are called the anterior (cranial) and posterior (caudal) neuropores. Anterior neuropore closes on day 25 and posterior neuropore on day 27.

Dorsal view of human neural groove: somites are balls of mesoderm that mature into the segmented axial skeleton. Each pair is added sequentially from head to tail down the length of embryo.

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16
Q

Wnt signalling is involved in induction of organisors and thus, the three germ layer formation. Wnt signalling is also involved in neural patterning, meaning posterior-anterior development.

How is Wnt influenced to cause neural patterning? What happens if Wnt is not influenced?

A

Wnt inhibitors (Dickkopf, Cerberus, Frzb, IGF) are made by dorsal anterior mesoderm and the organiser. This causes neural patterning.

For example, in Xenopus ectopic placement of Cerberus during early gastrulation gives rise to a secondary head structure (because Wnt was not inhibited).

17
Q

FGF and RA are also very important in anterior-posterior patterning.

To recap: Where are Wnt inhibitors, FGF (fibroblast growth factor) and RA (retinoic acid) produced that cause them to influence anterior-posterior patterning?

A

Wnt inhibitors are made at dorsal anterior mesoderm.

FGF is made at posterior mesoderm.

RA made by central mesoderm.

18
Q

Brain development from neural tube:

How are the forebrain, midbrain and hindbrain formed?

How does the forebrain form the cerebral cortex and how is spinal cord formed?

A

The anterior part of the neural tube divides rapidly to form three primary vesicles: forebrain, midbrain and hind brain.

Part of the forebrain curls up and around it will become cerebral cortex. The posterior part of neural tube forms the spinal cord.

19
Q

The relationship of embryogenic brain to adult brain:

  • Forebrain:
  • Midbrain:
  • Hindbrain:

How many layers does the brain have?

A
  • Forebrain: cerebral cortex, underlying white matter, corpus callosum, basal ganglia
  • Midbrain: vision, hearing, motor control, sleep/wake, arousal, temperature
  • Hindbrain:
    • Medulla - autonomic functions (breathing, heart rate, blood pressure)
    • Pons - brainstem (swallowing, bladder control, hearing, etc.)
    • Cerebellum - posture, balance

Brain has 6 layers: molecular layer, external granular layer, external pyramidal layer, internal granular layer, internal pyramidal layer, and fusiform layer.

20
Q

What is the function of radial glial cells?

Hoe are cortical layers formed?

A

Cortical neurons migrate along radial glial cells.

Cortical layers form in an ‘inside out’ sequence:

  • First cohort of neurons move from ventricular zone towards the pial surface to form preplate.
  • First migration wave of cortical plate neurons arrive in the middle of the preplate, splitting it into three zones.
  • More cortical plate neurons arrive in an ‘inside out’ sequence, with earliest-born neurons destined to become future layer 6 and the last-born layer 2.
21
Q

How can we visualise neurons during the early stages of development?

A

By using intermediate filament proteins as cell markers:

  • Neural stem cells express nestin.
  • Immature glial cells express vimentin.
  • Mature nerve cells express NF-H, NF-M, NF-L.
  • Mature glial cells express glial fibrillary acidic protein.
22
Q

Reelin is an extracellular matrix-associated glycoprotein. …-Retzius cells in the … zone have ascending processes that contact the pial surface and a horizontal axon plexus. They secrete ‘reelin’ which is essential for neuronal … .

Reelin binds to: … , apolipoprotein E receptor (ApoER2), … precursor protein (APP) and integrin receptors. … 1 (Dab1) binds with the cytoplasmic tails of the above receptors and becomes phosphorylated. This causes … signalling kinase cascades, which results in changes in gene expression and the … properties of neurons causing them to … .

A

Reelin is an extracellular matrix-associated glycoprotein. Cajal-Retzius cells in the marginal zone have ascending processes that contact the pial surface and a horizontal axon plexus. They secrete ‘reelin’ which is essential for neuronal migration.

Reelin binds to: VLDL-R, apolipoprotein E receptor (ApoER2), amyloid precursor protein (APP) and integrin receptors. Disabled 1 (Dab1) binds with the cytoplasmic tails of the above receptors and becomes phosphorylated. This causes downstream signalling kinase cascades, which results in changes in gene expression and the surface properties of neurons causing them to migrate.

23
Q

Reelin NULL and Dab1 NULL (scramler) consequence.

Adult neural stem cells in human brain locations.

A
  • Human Reelin (RELN) mutation has been linked to lissencephaly (lack of brain folds, fatal) and autism.
  • Neural stem cells locations: dentate gyrus of hippocampus + lining of lateral ventricles (subventricular zone).