Zusammenfassung
SUMMARY BBS2002 (including lectures and practicals)
- Kurs
- Hochschule
this is a summary of all the cases (with implemented lecture notes) and practicals
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Inhaltsvorschau
Case 1Prenatal neural development
Neurodevelopment is a term referring to the brain’s development of neurological
pathways that influence performance or functioning (e.g. intellectual functioning, reading
ability, social skills, memory, attention or focus skills). At week 5 the brain starts to
develop and at week 8 the cells are in place. After birth the brain starts to increase in
weight and that is due to the rapid formation of connections. First you have gastrulation,
in which the 3 germ layers are formed. Then the ectoderm becomes thickened and that
is called a neural plate. Then you have neurulation= the neural plate becomes the neural
tube and eventually the brain and spine.
STEPS:
1. The lateral edges of the neural plate become elevated and form neural folds. The
depressed region is then called the neural groove.
2. The neural folds then fuse in the middle and then move cranially/caudally.
- During fusion, the ends communicate via neuropores.
3. The neural tube is then formed at day 25 (cranially) and day 28 (caudally)
- The caudal part forms the spine and the thicker, cranial part forms the
brain.
4. Then neural crest cells begin to dissociate from their neighbors and undergo an
epithelial-to-mesenchymal transition, so it leaves the neuroectoderm and goes to
the mesoderm.
5. Crest cells from the trunk migrate via 2 ways after closure of the tube:
- dorsal pathway through the dermis, so they will enter the ectoderm
through holes in the basal lamina to form melanocytes in the skin and hair
follicles.
- ventral pathway through the anterior half of each somite to become
sensory ganglia, sympathetic and enteric neurons, Schwann’s cells, and
cells of the adrenal medulla.
6. Crest cells from the cranial folds migrate before closure of the tube to become
craniofacial skeleton, neurons from the cranial ganglia, glial cells and
melanocytes.
,After neurulation you have the three-vesicle stage in which the prosencephalon,
mesencephalon and rhombencephalon are formed due to differences in proliferation rate.
Then you have the five-vesicle stage in which the prosencephalon divides into the
telencephalon and diencephalon and the prosencephalon divides into the metencephalon
and myelencephalon.
Neurogenesis
Neurogenesis is the formation of neuronal structures. The telencephalon consists of two
layers: the ventricular zone and the marginal zone. The ventricular zone lines the inside
of each vesicle, and the marginal zone faces the overlying pia. Neurogenesis is divided
into 3 stages: proliferation, migration and differentiation.
1. Proliferation
The stem cells are in the ventricular zone and can proliferate via 2 ways:
- symmetrical: the stem cell produces 2 stem cell daughters that stay in the
ventricular zone (vertical cleavage). Happens early in development so that the
population of progenitors can expand.
- asymmetrical: the progenitor produces one differentiated daughter cell and
another stem-cell daughter cell (horizontal cleavage). Happens in later
development so that the daughter cell lying farthest away from the ventricular
surface migrates away to take up its position in the cortex, where it will never
divide again. The other daughter remains in the ventricular zone to undergo more
divisions
- early asymmetrical cell division: promotes increase neuron population
- later asymmetrical cell division: promotes glia production
The neurons proliferate in a choreography that is divided into 5 positions:
1. First position: A cell in the ventricular zone extends a process that reaches
upward toward the pia.
2. Second position: The nucleus of the cell migrates upward from the ventricular
surface toward the pial surface; the cell’s DNA is copied.
3. Third position: The nucleus, containing two complete copies of the genetic
instructions, settles back to the ventricular surface.
4. Fourth position: The cell retracts its arm from the pial surface.
5. Fifth position: The cell divides in two.
,Migration
Stem cells in the developing brain move along the surface of radial glial cells. These glial
cells are used as guides and extend from the inner (ventricular) to the outer (plial)
surfaces of the nervous system. The migration is regulated by cell adhesion molecules
(CAMs). The layering of neurons happens via an inside-first, outside-last rule. Cells that
migrate from the ventricular zone and leave the cell cycle at early stages give rise to
neurons that settle in the deepest layers of the cortex. Cells that exit the cell cycle at
progressively later stages migrate over longer distances and pass earlier-born neurons,
before settling in more superficial layers of the cortex.
The first cells to migrate to the cortical plate are those that form the subplate.
As these differentiate into neurons, the neural precursor cells destined to
become layer VI cells migrate past and collect in the cortical plate. This process
, repeats again and again until all layers of the cortex have differentiated. The
subplate neurons then disappear.
Differentiation
Proteins called notch-1 and numb migrate to
different poles of ventricular zone precursor
cells. When the neuron divides vertically, the
notch-1 and numb proteins are partitioned
symmetrically. However, when the cell divides
horizontally, notch-1 goes with the daughter
that will migrate away, while numb remains
with the cell that will divide again. Notch-1,
“unopposed” by numb, activates the gene
expression that causes the cell to cease dividing
and migrate away from the ventricular zone.
Notch regulates the fate of cells in the
developing cerebral cortex.
during prenatal development: notch signaling regulates self-renewal of developing and
adult neural stem cells. During (mostly) postnatal development, notch promotes
gliogenesis.
- 1st neuronal differentiation: primarily prenatal
- 2nd astrocyte differentiation: peaks around time of birth → increase in Notch
- 3rd oligodendrocyte differentiation → decrease in Notch
Glial cells: Notch promotes the generation of radial glial cells by activating members of
the Hes family of bHLH transcriptional repressors. Hes activates the expression of an
ErbB class tyrosine kinase receptor for neuregulin, a secreted signal that promotes radial
glial cell identity.
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