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Medical Science
Maurice Curtis

Lecture 3 Nervous System Development Tuesday, 23 July 2013 11:42 a.m. 5 Developmental processes: 1. Gastrulation 2. Induction 3. Neurulation 4. Fusion 5. Vesicle formation Gastrulation:  As function increases through the development of the organism fetus plasticity/renewal of the brain cell decreases. Highly specialised and functional cells are formed with limited if not no renewal potential. The brain has a relatively fixed function its entire life.  Proliferation of inner cell mass and migration to different regions.  The ectoderm forms the brain and CNS. Induction:  How different types of tissue form via influence of secreted growth factors from neighbouring tissue.  Main growth factors include BMP4 which works with chordin, noggin and FGF produced with by the nortochord.  The presence of chordin and noggin inhibit BMP4 action allowing the ectoderm to neuralise in the absence of BMP4 (anterior neuroectoderm)  The presence of FGF and BMP4 induces the formation of the spinal cord (posterior neuroectoderm) Neural tube formation:  The crest of the neural tube becomes peripheral nervous system while the neural tube itself becomes the central nervous system while the somites become vertebrates.  Failed closer of the anterior neural pore results in the lack of formation of the forebrain also known as anencephaly  Failed closure of the posterior pore results in the spina bifida. 3 vesicle stage:  Anterior vesicle: prosencephalon ---> forebrain  Mid vesicle: mesencephalon ---> midbrain  Posterior vesicle: Rhombencephalon ---> hindbrain 5 vesicle stage:  The differentiation from 3 vesicles to 5 vesicles occurs between 4 weeks (3 stage) and 6 weeks (5 stage). Results from some cells growing more than others causing flexure.  The prosencephalon differentiates into the telencephalon that will be the two cerebral hemispheres and the diencephalon which will form the thalamic regions. During this process the lateral and third ventricles will begin to form.  The Rhombencephalon differentiates into the metencephalon which will form the cerebellum and pons while the myelencephalon will form the medulla. During this differentiation the fourth ventricle and cerebral aquaduct will begin to form. Notes:  Is the most enlarged part of the human brain  Telecephalon differentiates into two hemispheres that form a super ventricle do to the fact that there is more space than tissue present. 8 stages of cortical development: 1. Neural proliferation 2. Neural migration 3. Neural differentiation 4. Axonal growth 5. Dendritic growth 6. Synaptogenesis 7. Myelination 8. Neuronal death 1. Neural proliferation:  Begins as soon as neural tube closure occurs, the cells migrate out in all directions along long distance fibres that have formed spokes. The radial fibres (glia) are anchored in the ventricular zone and act as a scaffolding allowing cells to reach and form the cortex.  The lateral ganglionic eminence: responsible for formation of cortical and all neural cells. Located inside the neural tube and has the greatest proliferative ability.  The medial ganglionic eminence:  Stem cells stay within the ventricular zone where one mother cell has over 10,000 daughter cells.  All neurons are prenatally made at a rate of thousands/minute. During the 8-12 week stage there is massive proliferation. 2.Neural cell migration:  Radial migration: Non-diving cell layer migrates from the ventricular layer via the long distance radial glia cells creating a radial inside-out pattern. The cells move along the glia by the leading process, wrapping around the glia cells.  The radial glia disintegrate after week 12, they are important as they position the divided cells correctly in cortex.  Conexin26 acts as the cue for cells to move along radial fibres as well as the presence of actin and intermediate filaments.  Locomotion: movement of the entire cell as a leading and trailing process involving the movement of cytoskeletal proteins. Favoured as is more energetically favourable.  Nuclear translocation: cell becomes elongated as it increases the cell contents and components. More energy intensive.  Tangential migration: 1 cell uses the other cells as cues on where to migrate, very few use this migration pattern, mostly radial. 2.b.Cortex positioning and development:  Position within the cortex and the cells function is determined by the time of birth of the cell. The brain is very time sensitive, not a critical as some organs but not reaching certain stages by the appropriate time will effect later development.  Cajal-retzius cells are located in the marginal zone, give the divided cells cues on when to dismount from the radial cells in the cortical zone. Disruption of the Cajal-retzius cells causes lack of organisation in the cortical zone as cells do not known when to disengage from the glia. The signal that the Cajal-retzius cells use is Reelin.  New cells migrate through the already established layers to create 6 distinct layers in the cortex, the cells that are born and migrate first form layer 6, the deepest layer, while the cells born last form lay
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