5. neural development

• Notochord and somites
• Mesoderm


  One of the three primary germ layers formed during gastrulation
• Derivatives of mesoderm - embryonic

  • Chordamesoderm
  • Paraxial mesoderm
  • Intermediate mesoderm
  • Lateral plate mesoderm

  
• Derivatives of mesoderm - adult

  • Axial skeleton
  • Striated musculature
  • Subcutaneous tissue and skin
  • Urinary system
  • Gonads
  • Digestive tract wall
• Notochord


  A flexible rodlike structure that is the main longitudinal structural element in the early vertebrate embryo
• Notochord


  • Represents a primitive form of cartilage
  • Serves as the axial skeleton of the embryo until other elements (eg vertebrae) form
  • In later development, it becomes part of the spinal column and forms the centre of the intervertebral discs
• Notochord formation from mesoderm

  1. Chordamesoderm cells develop a thick extracellular sheath and a vacuole

  2. The vacuole produces osmotic pressure that gives the notochord its rod-like appearance and supports embryonic elongation

  
• Role of notochord in patterning

  • Patterns the neural tube by signaling the formation of the floor plate
  • Reinforces and maintains events begun during gastrulation, such as left-right asymmetry and organisation of cardiac and pancreatic development
• Notochord development in humans

  1. Chordal tissue forms the chordal plate by bonding with the endoderm, then separates to form the complete notochord

  2. Notochord development occurs around Days 19-25 of human embryonic development

  
• Notochord development


  Induces the formation of the neural plate (start of neurulation)
• Paraxial mesoderm


  Forms cylinder-shaped segments (somites) in the vicinity of the neural tube and notochord
• Somitogenesis


  1. Paraxial mesoderm extends caudally, budding off somitomeres that compact into discrete somites

  2. Somite identity and fate depends on their location along the anterior-posterior axis
• Somites


  • Responsible for segmental organisation of the embryo
  • Contain precursor cells for the axial skeleton (sclerotome), striated musculature (myotome), and subcutaneous tissue/skin (dermatome)

  
• Somite number is an accurate measure of embryonic age in humans
• Intermediate mesoderm


  Forms the urogenital crest, the origin of the kidneys and gonads
• Lateral plate mesoderm


  Composed of somatic and splanchnic layers that form the body wall and digestive tract wall, respectively
• The urinary and gonadal/genital systems are developmentally linked
• The nervous system is composed of the central nervous system (brain and spinal cord) and the peripheral nervous system (ganglia and peripheral nerves)

  
• Cells of the central nervous system

  • Neurons
  • Glia (astrocytes, oligodendrocytes, ependymal cells, microglia)

  
• Neurons


  • Many sizes, shapes and varieties (motor, sensory, interneurons)
  • Dendrites (receive signal)
  • Cell body (soma)
  • Axon (transfers signal)
  • Axon terminals (send signal to next cell)
  • Synapse (includes axon terminal)

  
• Glia


  • Astrocytes (star-like shape, critical supportive role for neurons)
  • Oligodendrocytes (myelinate axons)
  • Ependymal cells
  • Microglia (immune cells)

  
• Signalling in the central nervous system

  Neurons signal to each other at synapses, usually via chemical signals (neurotransmitter release and binding to receptors)
• Oligodendrocytes


  • Send out processes that are wrapped around axons many times to myelinate and insulate them
  • A single oligodendrocyte myelinates multiple segments or axons

  
• Astrocytes


  • Involved in nutrient supply
  • Clean up at synapse
  • Phagocytose cell debris
  • Structural role
• The nervous system develops from the ectoderm germ layer
• Neural induction


  Signals converge on the middle region of the ectoderm and induce it to become neural tissue

  
• Neurulation


  1. The folding up of the neural plate to form the neural tube

  2. The brain and spinal cord maintain a tube-like structure with a fluid filled space in the centre throughout life

  
• Neurulation


  • Apical constriction of actin filaments can help drive elevation of the neural folds
  • Differential expression of cadherins can help create separation of epidermal ectoderm from the neural tube

  
• The neural tube closes at about the middle first, then zippers up in both directions, with open neuropores on both ends that need to be closed for normal development
• Failure of the neural tube to close results in neural tube defects like anencephaly (open cranial neuropore) and spina bifida (open caudal neuropore)
• Regions of the central nervous system

  • Forebrain (telencephalon and diencephalon)
  • Midbrain
  • Hindbrain
  • Spinal cord

  
• Patterning of the brain and spinal cord

  • Signalling is vital, with growth factors like BMPs, Fgfs, Wnts and Shh acting in a concentration-dependent manner
  • Transcription factors control the type of neuron produced

  
• If you placed sonic hedgehog (Shh) ectopically lateral to the neural tube instead of ventral to it


  It could induce a second set of motor neurons
• Neurogenesis - production of neurons

  1. Proliferation of progenitor cells via symmetrical division to produce more progenitors

  2. Asymmetrical division to produce neurons and maintain progenitors

  3. Intrinsic and extrinsic mechanisms regulate asymmetrical division

  
• Asymmetrical cell division


  • Asymmetric division type I - generates another apical progenitor and a neuroblast (neuron)
  • Asymmetric division type II - produces a basal or intermediate progenitor, which divides at least once prior to differentiation into neurons
• Increased basal progenitors correlates with presence of gyri (bumps on brain surface)
• Neuron migration and organisation

  1. Neurons move away from the ventricular layer

  2. Formation of layers: ventricular layer, mantle layer/intermediate zone, marginal layer
• Spinal cord organisation remains straightforward, with alar plate (dorsal), basal plate (ventral), ventricular layer, mantle layer/intermediate zone, and marginal layer
• The fluid filled space in the neural tube continues into adulthood as the ventricles in the brain, containing cerebrospinal fluid