Samenvatting
Summary All cases BBS2002
- Instelling
- Maastricht University (UM)
All the cases of BBS2002. The cases are extensive and made according to the resources provided by the course.
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Voorbeeld van de inhoud
Case 1 – The developing nervous system1. Briefly repeat the formation of the neural system before birth → more cellularly
Embryonic neurodevelopment is derived from the ectoderm, which is responsible for
the formation of our central nervous system, peripheral nervous system and
epidermis.
Gastrulation begins at around day 13, reorganizing the single-layered blastula into a
multi-layered structure known as the gastrula.
During this phase, the primitive streak develops on the epiblast around day 15. This
streak grows into the primitive groove and eventually the node. During invagination,
the epiblast cells migrate into the streak, replacing the hypoblast while forming three
distinct germ layers:
- Ectoderm: epiblast cells that did not migrate
- Mesoderm: cells from the 2nd wave of ingression
- Endoderm: epiblast cells from 1st migration
By day 16 gastrulation is complete.
Neurulation begins with the formation of the notochord. This is a structure made from
cells that formed the primitive pit. The notochord induces neural plate formation in the
ectoderm above it, using paracrine signalling. Ectoderm develops normally in the
presence of BMP signals, but the notochord releases Chordin, Noggin and Follistatin,
which inhibit BMP. In BMP’s absence, the ectoderm develops into the neural plate, since
the uninfluenced ectoderm differentiates into neuronal cells.
Initially, the neural plate is only a single layer of neuroectoderm cells. Rapid
proliferation of these cells, especially at the lateral margins, creates a neural groove
bordered by neural folds. Continued cell division enlarges the neural folds, and they
,eventually fuse to form the neural tube. The neural tube is open at both ends, the
anterior and posterior neuropores. It gives rise to the brain and the spinal cord. The
lumen of the neural tube, the neural canal, becomes the four ventricles of the brain and
the central canal of the spinal cord.
The cells that line the inside of the neural tube are called neuroepithelium, and they
will eventually form the neurons in the brain and spinal cord. In addition, cells within
the neuroepithelium also give rise to a specialized group of migratory cells, called the
neural crest → these cells leave the neural tube soon after it has closed, and they
migrate away to form a wide variety of peripheral tissues, such as the sympathetic and
parasympathetic ganglia. Inside the tube, the cells continue to proliferate rapidly, though
the rate varies along the tube depending on which CNS structures are being formed.
Ventricular system
The structures of the ventricular system are derived from the neural canal, the center of
the neural tube. The irregular rate of proliferation in the rostral area of the neural tube
leads to the formation of 3 primary vesicles:
1. Prosencephalon
2. Mesencephalon
3. Rhombencephalon
The 5 secondary vesicles are divisions of the primary vesicles, but the mesencephalon
doesn’t divide.
- The prosencephalon (forebrain) → divides into the telencephalon and
diencephalon.
- The rhombencephalon (hindbrain) → divides into the metencephalon and the
myelencephalon.
As the neural canal expands dorsally and laterally, the fourth ventricle is created.
However, the regions of the neural canal that does not expand remains superior to the
fourth ventricle and forms the cerebral aqueduct.
,This progressive patterning and subdivision of the neural tube is regulated by secreted
signals. The promotion of ectodermal cells into neural ells relies on two major proteins:
- Inductive factors: initially secreted from the mesoderm and endoderm along the
neural plate. Later, once the neural tube is closed, these signals are secreted from
secondary organizing centres in the neural tube.
- Surface receptors: allow the cells to react to these inductive factors
Activating such a receptor will trigger the expression of certain genes that encode
intracellular proteins and will push the cells into the neural pathway development. The
ability of a cell to respond to inductive signals is called the competence, which thus
doesn’t only depend on signals to which it is exposed, but also whether their prior DNA
expressions have caused the required receptors/molecules or not.
2. Proliferation and differentiation of stem cells in the brain (neurons)
Neuronal structure develops in 3 major stages: cell proliferation, cell migration and
cell differentiation. The development occurs in the walls of the secondary vesicles. The
walls consist of two layers, called the ventricular zone and the marginal zone.
- Ventricular: inside of each vesicle
- Marginal: faces the overlying pia.
Within these layers of the telencephalic
vesicle, a cellular ballet is performed that
gives rise to all the neurons and glia of the
visual cortex.
1. A cell in the ventricular zone extends a
process that reaches upward toward the pia.
2. The nucleus of the cell migrates upward
from the ventricular surface toward the pial
surface: the DNA is copied.
3. The nucleus, containing two complete
copies, settles back to the ventricular surface.
4. The cell retracts its arm from the pial
surface.
5. The cell divides in two.
, These dividing cells, the neural progenitors that give rise to all the neurons and
astrocytes of the cerebral cortex, are called radial glial cells. Early in the embryonic
development, the glial cells number in hundreds and they give rise to the billions of
neurons in the adult brain. To give rise to these neurons, the multipotent stem cells
divide to expand the population of neural progenitors via a process called symmetrical
cell division. Later in development, asymmetrical cell division is the rule → one
daughter cell migrates away to take up its position in the cortex, where it will never
divide again. The other daughter cells remains in the ventricular zone to undergo more
divisions.
How is a cell’s fate determined? Every daughter cell
has the same genes. The factor that makes one cell
different from another is the specific genes that
generate mRNA and proteins. thus, cell fate is
regulated by differences in gene expression during
development. In symmetrical cleavage, Notch-1 and
Numb are divided evenly. In asymmetrical cleavage,
the uneven distribution of enzymes and
transcription factors causes differentiation.
Mature cortical cells can be classified as glia or
neurons, and the neurons can be further classified
according to the layer in which they reside, their
dendritic morphology and axonal connections, and
the neurotransmitter that they use. Multiple cell
types can arise from the same precursor cell
depending on what genes are transcribed during
early development.
The ultimate fate of migrating daughter cell is
determined by a combination of factors,
including the age of the precursor cell, its
position within the ventricular zone, and its
environment at the time of division.
- Cortical pyramidal neurons and
astrocytes derive from the dorsal
ventricular zone.
- GABAergic inhibitory interneurons
and oligodendroglia derive from the
ventral telencephalon.
The first cells to migrate away from the
dorsal ventricular zone are destined to reside
in a layer called the subplate, which
eventually disappears as development
proceeds. The next cells to divide become
layer VI neurons, followed by the neurons of
layers V, IV, III and II.
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