week 5

• Neural crest cell (definition)


  A group of cells that originate at the dorsal part of the vertebrate neural tube

  
  

  It can give use to a wide range of differentiated cell types

  
  

  Referred to as the 'fourth primary tissue
• Why are a bunch of cells from the dorsal neural tube so important to vertebrate life?

  Cell population with one of the broadest development potential

  
  

  It can make cartillage and bone, neurons, connective tissue, neurons, pigment cells
• What is the origin of neural crest cells (NCCs)

  Ectoderm

  
  

  Neural crest forms at the juxtaposition of the non-neural and the neural ectoderm
• How do we know so much about NCCs?

  Researcher on chick quail chimeras

  
  

  Graft cells from a quail, add them to a chick and see where the cells end up (through staining) or what they form into
• Chick quail chimeras result

  The chick that formed with some quail cells went on to form part of the wing. It formed the pigment cells of the wing (not the structure itself)
• Properties of NCCs


  Multipotent stem cells

  They can differentiate into many cell types

  Show remarkable migration pathways through the developing embryo
• Multipotent


  Can't reproduce an entire embryo, but can form many different cells of the embryo

  
  

  The diversity of the cells decreases as the migration proceeds
• Cells that NCCs can become (and what makes it become that)

  Sensory neuron

  Autonomic neurons

  Schwann cells

  
  

  
  

  ***
• Are NCC progenitors really multi-potent? Limitation of grafting experiments


  Two possible options

  
  

  They are different cells that were grouped together so couldn't tell them apart, but could only form one fate. Or have a stem cell that can form all of the cell types.

  
  

  Grafting cells cannot tell this apart, need another test
• How would you test if NCC progenitors are really multipotent?

  1. Can genetically label individual NCCs. Labels all of the NCC with different fluro markers.

  2. Trace what those cells become in vivo.
• Do NCCs lose their potency after leaving the neural tube?

  Most NCCs are still multipotent even after they have left the neural tube

  
  

  So this suggests that neural crest stem cells in vivo
• 4 main domains of NCC

  Cranial

  Cardiac

  Vagal

  Sacral
• Cranial NCCs


  Important cranial NCC derivatives include (of the face) = cartilage, bone, connective tissue.

  
  

  They form borns through intramembranous ossification
• Cardiac NCCs


  Melancocytes

  Septum that separates the pulmonary artery from the aorta

  Muscular-connective tissue of pharyngeal arches
• Vagal and sacral NCCs

  Derivatives include the parasympathetic ganglia (gut associated neuronal cells)

  
  

  Important for peristaltic movements of the bowel
• Trunk NCCs


  Important trunk NCC derivatives include sympathetic ganglia, Schwann cells, adrenal gland medulla, pigmented cells of the skin
• Migration pathways of NCCs (steps)

  1. Following induction, NCC undergo epithelial to mesenchymal transition

  2. NCC delaminate from the neural folds and start their migration

  3. Migration is determined by intrinsic properties and external environment
• What determines migration pathway?

  Intrinsic properties (things in the cell). e.g. adhesion molecules (amount of them change as cell migrates to final destination)

  
  

  External environment

  e.g. extracellular matrix
• Trunk NCCs cell pathways

  Can take very different migratory pathways

  
  

  Path 1 cells travel ventrally through the anterior sclerotome = become Schwann cells, sensory neurons

  
  

  Path 2

  
  

  ***
• Defects associated with NCCs

  - Pigmentation defects (trunk and cranial NCC)

  - Peripheral nerve tumours

  - Defects in vagal NCC, enlarged colon
• Where do cell junctions occur?

  Between two cells or between a cell and the extracellular matrix
• Extracellular Matrix (ECM) may form...

  - an insoluble barrier or connection between tissues

  - a loose network in which cells are scattered

  - a substratum which cells bind to and form a sheet (e.g. epithelial cells on a basal lamina)

  - a substratum over or through which cells migrate
• Types of ECM


  Fibrous proteins (mostly collagens)

  Proteoglycans and glycosaminoglycans

  Glycoproteins
• Why are junctions important?

  Important in maintaining adult tissues, development of tissues
• Epithelium cell junctions


  It forms sheets of cells, serve as a barrier (selectively permeable)

  
  

  Strong attachments between cells - intracellular junctions
• Types of junctions


  Tight junctions

  Adherens junctions

  Desomeres

  Gap junctions

  Hemidesomosomes

  Focal adhesions
• Tight junction


  Completely encircles the cell, provides a seal to stop molecules moving inbetween
• Function of tight junctions


  Prevent the passage of molecules and ions through the space between cells

  
  

  They block the movement of integral membrane proteins between the apical and basolateral surfaces of the cell
• Gap junctions


  Provide direct cytoplasmic connection between cells

  
  

  They provide ion flow between cells, allowing membrane potential to pass from cell to cell

  
  

  Connexins form channels

  
  

  Most cells use this to communicate

  
  

  Important for heart rate
• What makes up gap junctions?

  Made of six copies of transmembrane proteins called connexins
• Adherens junctions


  Aka Zonula adherens

  
  

  Provide some adhesion between cells, encircles the cell

  
  

  Connect to actin microfilaments (in a bundle)

  
  

  Actin filaments are joined by cadherins
• Hemidesmosomes


  Provide adhesion from cell to extracellular matrix, connect intracellularly to intermediate filaments
• Function of adherens junctions

  Provide STRONG mechanical attachments between adjacent cells

  
  

  (e.g. cardiac muscles, epithelial)
• How does the epithelial sheet change shape?

  Adherens junctions

  
  

  Epithelial sheet is invaginated by tightening adhesion belts with associated actin filaments, pinches off from overlying sheet of cells
• Focal adhesions


  Allow adhesion of the cell to extracellular matrix, where actin filaments insert into plaques on the cytoplasmic surfaces
• Integrins


  Transmembrane proteins, they bind to extracellular matrix molecules

  
  

  Link actin cytoskeleton of a cell to various external structures
• Which of the following proteins is NOT involved in cell adhesion (to other cells or the extracellular matrix)?

  Connexins

  
  

  (the ones that are = integrins and cadherins)
• Desosome


  Holds two cells tightly together via their attachment to intermediate filaments in the cytoplasm
• Hemidesomosome


  Connects the basal surface of an epithelial cell to the underlying basal lamina
• Why are adhesion molecules important in development?

  They organise cells into complex tissues and maintain boundaries

  
  

  Therefore changes in cell adhesion result in reorganisation of cells