Unit 4: Evolution & Functional Org of Nervous System

• Cell cleavage: process in which number of cells in a developing embryo gets multiplied through cell division

  1. fertilized egg
  2. 2 cell stage
  3. 4 cell stage
  4. 8 cell stage
  5. morula
  6. blastula
  7. early gastrula
  8. gastrula
• 14 day rule:

  • rule that human embryos older than 14 days should not be produced in lab or subject to research.
  • at 14 days, chemical signals from mother are expected
  • no biological identity before this.
• Gastrulation consists of: endoderm, mesoderm, and ectoderm
• endoderm (internal layer) makes up:

  • lung cells
  • thyroid cells
  • digestive cells
• mesoderm (middle layer) makes up:

  • cardiac muscle cells
  • skeletal muscle cells
  • tubule cells of kidney
  • red blood cells
  • smooth muscle in gut
• ectoderm (external layer) make up:

  • skin cells of epidermis
  • neuron on brain
  • pigment cells
• neurulation:

  • occurs 3 weeks after fertilization
  • forms the 3 primary tissue layers
  • the remaining structures become the Chorion-allantois – providing the interface between the embryo and the mother. 
• Signalling factors from the notochord trigger ectoderm cells to proliferate and differentiate into the Neural Plate, which later forms the neural tube and neural crest.
• The neural tube forms when the lateral edges of the neural plate fuse along the midline
• Failure at the posterior end can lead to spina bifida, often linked to insufficient maternal folate intake, while failure at the anterior end can result in anencephaly, which is typically non-viable.
• Temperature spikes during pregnancy, such as high fevers or exposure to hot tubs or saunas, have been suggested as potential causes of anencephaly
• expansion of the prosencephalon (forebrain):

  • prosencephalon
  • telencephalon
  • cerebral hemispheres
  • diencephalon
  • thalamus / subthalamus / hypothalamus
• expansion of the mesencephalon (midbrain):

  • mesencephalon
  • midbrain
• expansion of the rhombencephalon (hindbrain):

  • rhombencephalon
  • metencephalon
  • pons
  • cerebellum
  • myelencephalon
  • medulla
• Neural Tube to Brain:

  • Proliferation: Cell birth – Cell Cycle – Mitosis
  • Migration: Cell movement – Motility – guidance
  • Differentiation: Maturity – Wiring – Dendrites/Axons - Guidance
• proliferation (8-20 weeks after fertilization):

  • Neurogenesis occurs in the walls of the 5 fluid filled vesicles
  • Ventricular Zone
  • Radial glial cells give rise all neurons
  • 250,000/minute between months 2-5
  • Asymmetric cell division
• Helpers of Neuronal Migration:

  • Radial Glia: guide neurons to destinations using special connection (N-cadherin) to help neurons move and stay in touch
  • Semaphorin 3a (in outer layer of the brain): signals to let neurons know they reach the correct place.
  • Cajal Retzius Cells: release reelin which tells neurons to stop moving. prevents overshoot
• Cortical Development: The brain's outer layer, called the cortex, has up to 6 layers. These layers form in a specific order, like stacking pancakes.
• 1. Inside-Out Development: Imagine you're making that cake from the inside out. Layer 6 forms first, then layer 5, then layer 4, and so on. It's like adding layers of different flavors from the center to the outside.
• Radial Migration: cells move from the bottom to the top

  • about 75% of brain cells use this "radial migration" to reach their layers
• Subventricular Cells: cells in the bottom layer of the brain.

  • in charge of producing more brain cells for the outer layers
• Horizontal Migrating Cells: cells that move sideways through the layers.
• Factors that help guide Radial glia and Neurons:

  • timing and location: knowing where they're going
  • rising and falling levels: brain cells follow signals that get stronger or weaker over time
  • concentration gradient: changes in concentration
  • different sources: signaling from various parts of the brain
• Oligodendria: These cells start their journey from the ventral region
• GABAergic Neurons: They begin their journey from the middle,
• Neurons expressing high PAX6 gene/low EMX2 gene tend to head toward the front of the brain.
• Neurons with low PAX6/high EMX2 gene prefer to head toward the back of the brain
• When there are equal amounts of PAX6 or EMX2 genes, neurons tend to settle in the middle of the brain
• Semaphorin 3a is high near the outer layer of the brain (pial layer) and low near the inner layer (ventricular layer).
• Semaphorin 3a attracts the branches of pyramidal cells called apical dendrites towards the outer layer of the brain.
• Semaphorin 3a repels the axons of these cells, preventing them from going in the wrong direction.
• Methylation = on/off switch of genetics
• Histone acetylation = volume knob of genetics (how strong)
• Neural precursors expressing Pax-6 gene are found anteriorly. 

  • Critical for formation of anteiro cortex, the eye, and for proper direction of axonal growth in the forebrain.
• Fetal Development (20-38 weeks)

  • Elaboration of cortical and subcortical structures, major axonal pathways established, including the thalamocortical pathway
  • Folds (sulci) and ridges (gyri) adaptation to huge brain growth needed to occur in small heads (so we could fit through birth canal)
• Differentiation:

  • Neurons are responsible for the transport and uptake of neurotransmitters - chemicals that relay information between brain cells
  • Depending on its location, a neuron can perform the job of a sensory neuron, a motor neuron, or an interneuron, sending and receiving specific neurotransmitters.
• In the developing brain, a neuron depends on molecular signals from other cells, such as astrocytes, to determine its shape and location, the kind of transmitter it produces, and to which other neurons it will connect.
• CAMs (Cell Adhesion Molecules)

  • like molecular glue.
  • keeps growing axons stuck together in groups in a process called fasciculation
• Laminins:

  • signal for other cells.
  • Get recognized receptors called integrins.
  • When integrins bind to laminins, it extends the axon and helps find its way to its destination and helps with growth and guidance of the nerve cell
• Early fetal period = neurons complete migration to 6 layers of cortex (day 108/week 16)