Block B

• Eukaryotic organisms


  • Protists - simplest, single-celled eukaryotes, but they still carry out life functions and show division of labour among the various cell structures
  • Metazoans - multicellular animals that have cells specialised for particular functions. With division of labour, the functions of life are separated
• Body plan


  • The evolution of animals have engineered more and more complex body plans
  • Radial and bilateral symmetry have evolved
  • Bilateral symmetry is associated with cephalisation, the differentiation of a head
  • Nervous tissue, sense organs, and often the mouth are located in the head
  • Advantageous for organism to move its head first - directional movement
  • Elongation along anteroposterior axis
• Coelomates


  • Have evolved to have a body cavity entirely within the mesoderm (coelom)
• Germ layers


  • Endoderm (internal layer)
  • Mesoderm (middle layer)
  • Ectoderm (external layer)
• Endoderm


  Alveolar cells, thyroid cells, pancreatic cells
• Mesoderm


  Cardiac muscle cells, skeletal muscle cells, tubule cells of kidney, RBC, smooth muscle cells (gut)
• Ectoderm


  Skin cells of epidermis, neuron on brain, pigment cells
• Body cavity


  • Isolation of organs for physiological independence
  • Flexibility when moving so organs don't rip apart
  • Separate organs cushioned against damage by fluid-filled cavities (also for separation and flexibility)
  • Prevents organs from sticking to each other and forming a giant mass - cells like to intermingle
• Embryonic development I: making stem cells

  1. Fertilisation restores the diploid genome

  2. Fertilising spermatozoon penetrates egg cell to begin the process of wiping out the memory of our parents - resetting the clock/starting afresh (wiping their environmental experience)

  3. Fertilisation -> first cleavage (Zona pellucida) -> 2 cell stage -> 4 cell stage -> 8 cell stage -> morula -> 128 blastocyst -> implantation and placenta formation (day 7)

  4. Cleavage is the division of cells in the early embryo. It undergoes rapid cell divisions with no significant growth to produce a cluster of cells the same size as the original 'zygote', filling the Zona pellucida, to form a Morula

  5. Blastocyst is a structure containing 128 cells. Its an inner cell mass ('embryoblast') that goes on to form the embryo proper

  6. The inner cell mass forms embryonic stem cells - beginnings of cell differentiation

  7. The outer cell mass ('trophoblast') goes on to form the placenta

  8. Trophoblast is the layer before the zona pellucida (which degenerates, making the trophoblast the outermost layer)
• Pluripotent stem cells (PSC)

  • Theoretically gives rise to every cell type in the animal body proper
  • It has the ability to proliferate indefinitely
  • It's the first recognised cell type in teratocarcinomas ('monster')
  • PSC have 3 lineages - mesoderm, endoderm and ectoderm
• Embryonic development II: breaking symmetry


  1. Implantation provides direction to the symmetrical lump of cells

  2. Blastocyst 'hatches' by shedding its outer layer, to expose the bare trophoblast cells to the uterine wall (day 7) (attachment - beginnings of placenta)

  3. The uterine wall is prepared for implantation each month under hormonal control

  4. The trophoblast begins to thicken as it begins to implant and form the placenta

  5. The embryo is fully embedded after 10 days

  6. Placenta formation sets up a direction to the embryo - distance from placenta

  7. Syncytial trophoblast - attached to placenta wall, invades to gain nutrients

  8. Cellular trophoblast - remains in embryo

  9. Once attachment is complete, it begins its nutrient supply from mother. Embryo development begins
• Embryonic development IIIa: blast cell layers

  1. Amniotic cavity formation and the appearance of 2 cell layers begins when the inner cell mass (ICM) pulls away from the trophoblast to form a hollow amniotic cavity

  2. The ICM forms a flat disc with 2 layers: Epiblast - dorsal, next to amniotic cavity (back of embryo), Hypoblast - ventral, facing yolk sac (front of embryo)

  3. Development occurs inside the yolk sac

  4. Anatomical directions are defined and symmetry is broken
• Embryonic development IIIb: 'gastrulation'

  1. Gastrulation defines the cell layers (-derms) and body shape

  2. The epiblast layer undergoes a complex rearrangement to form the germ cell layers

  3. Gastrulation movement: Some epiblast/ectoderm cells begin to migrate inwards toward the primitive streak, They move through the layer towards the hypoblast (primitive endoderm). The first cell through become the definitive endoderm, The next cells through form the intermediate layer, mesoderm, This movement progresses tail to head (caudal to cranial)

  4. 3 "germ" tissues: Ectoderm - epidermis, hair, nails, skin, brain and spinal cord, neural crest, Mesoderm - notochord, somite, intermediate mesoderm and lateral plate mesoderm, Endoderm - epithelial lining and glands of digestive and respiratory tracts
• Embryonic development IV: notochord formation

  1. Epiblast migration through the primitive pit forms a line towards the 'head'

  2. Notochord maturation: Its a rod defining the body axis and is the future site of the vertebral column, Acts as "organiser" to set up and coordinate the body plan
• Embryonic development V: neurulation

  1. Formation of the brain and spine: The notochord induces a fold in the overlying epiblast/ectoderm which pinches off to form a neural tube, Notochord signal converts the overlying ectoderm to become the neural plate

  2. Neural groove formation: Associated neural crest cells, Mesoderm begins to differentiate next to notochord, into 3 regions: somites - 40 pairs of body segments (repeating units) by end of week 4, Intermediate mesoderm - just lateral to somites, Lateral plate - splits to form coelom ("body cavity")

  3. Closure of neural tube beings at the end of week 3 and is complete by the end of week 4 (folic acid important here), 'Zipped' cranially (eventually brain) and caudally (spinal cord), Neural crest cells form sensory nerve cells and other structures

  4. Spina bifida is a condition caused by incomplete neural tube closure, exposing the spinal nerve, Most effective way to prevent this is to take folic acid/folate supplements before and during pregnancy (assists in metabolic function/mechanism of tube closure)

  5. The formation of a fold at the top of the neural tube dictates the appearance of 2 hemispheres of the brain
• Embryonic development VI: somite formation and segmentation


  1. The body plan appears by the end of week 4. The embryo undercutting is complete

  2. Somites have subdivided into sclerotome, myotome, and dermatome, which forms the vertebrae, skeletal muscles, and dermis respectively (body coelom is present)

  3. Segmentation is often clear in organisms like insects but in humans its more difficult to see. Its most obvious in mesoderm derivatives - dermatome, myotome, sclerotome

  4. Segmentation in humans is clear when there's spinal injury: Cervical segments - C5, C6, C7, C8, Thoracic segments - T1, T3-3rd, T4 (4th and 5th interspace), T6, T10, T12, Lumbar segments - L2, L3, L4, L5, Sacral segments - S1, S2, S3, S4, S5
• Cell differentiation


  1. Cells in isolation undergo differentiation, they started as a pluripotent stem cell in the blastocyst, but over time became more specialised until they reached their terminally differentiated form - heart muscle, neurone, liver cell

  2. There's a 'programmed' path to their specified form/fate

  3. This is normally a 'one-way' road as cells don't revert to pluripotency naturally

  4. Early on in development, before the cells have been programmed. Each single cell has all the information and ability to become the adult organism, Transplanted cells adopt the form appropriate for their new home

  5. Later on in development, the cells become specified/committed, Cells taken from different parts of an embryo remember where they came from and differentiate accordingly - "specified", Dissection of an embryo into quarters at this point would result in the quarters developing along the lineages that they would've produced
• Tissue differentiation


  1. Local cellular interactions that organise tissues

  2. Long-range 'morphogen' signals that determine the orientation of the embryo and its specific regions, It diffuses along the axis and gets more dilute as its progresses

  3. Cellular responses to these 2 signals that cause migration and specific differentiation processes to be irreversibly started

  4. Cell interactions: Mixtures of different cell types organise into regional embryo-like structures (like-with-like cell sorting), Cell adhesion often drives this - proteins expressed on the surface of cells that like to stick to the same molecules on other cells (homophilic interactions - same catenins/cadherins)

  5. Generating an axis (head-tail): morphogen gradients, Morphogen - molecule secreted that induces cell fate decisions in recipient cells in a concentration gradient-dependent long-range manner, It requires production from a point source, long-range distribution, reception and interpretation by cell, Interpretation is context-dependent, depending on the amount received and type of cell, Wolpert's "French flag" model 1: Cells sense quantity of morphogen and compare it to 2 programmed thresholds (LOTS, SOME, LITTLE BIT) and respond to that level with specific differentiation/behaviour, Wolpert's "French flag" model 2: Same idea as the first but a YES/NO logic response of cells: YES+NO, NO+YES, NO+NO, The concentration of activin determines the type of cell (toad embryo experiment)

  6. Morphogen gradient on anterior-posterior patterning of the limb: The 'zone of polarizing activity' at the posterior end of the limb bud secretes sonic hedgehog, which forms a gradient along the anterior-posterior axis
• Homophilic interactions


  • Cells like to stick to the same molecules on other cells
• Generating an axis (head-tail)

  Morphogen gradients
• Morphogen


  Molecule secreted that induces cell fate decisions in recipient cells in a concentration gradient-dependent long-range manner
• Morphogen gradient interpretation


  1. Production from a point source

  2. Long-range distribution

  3. Reception

  4. Interpretation by cell
• Morphogen interpretation


  Context-dependent, depending on the amount received and type of cell
• Wolpert's "French flag" model 1

  Cells sense quantity of morphogen and compare it to 2 programmed thresholds (LOTS, SOME, LITTLE BIT) and respond to that level with specific differentiation/behaviour
• Wolpert's "French flag" model 2

  Same idea as the first but a YES/NO logic response of cells: YES+NO, NO+YES, NO+NO
• Concentration of activin


  Determines the type of cell (toad embryo experiment)
• Morphogen gradient on anterior-posterior patterning of the limb

  1. The 'zone of polarising activity' (ZPA) secretes a morphogen that sets up the thumb-to-little-finger organisation of the hand

  2. When ZPA is grafted to the anterior limb bud mesoderm, duplicated digits emerge as a mirror image of the normal digits

  3. Shh (sonic hedgehog) can reproduce this - morphogen
• Injection of Wnt or Nodal morphogens

  Can induce a secondary axis
• Wnt8


  Induces a complete axis
• Nodal


  Induces a partial axis
• Nodal and lefty


  Genes that show unequal expression between the LHS and RHS of the embryo
• Situs inversus - body organs are swapped over (left and right are mixed up)
• Morphogens have set up a basic plan of the body and the cells are responsible for interpreting and acting on those signals
• Morphogen receptors


  Like Patches for Shh signal to the nucleus to initiate appropriate differentiation programs within the cell
• Homeotic genes


  Drosophila mutants were discovered with bits of bodies mixed up. Mutation that causes transformation of an area of the body into another area.
• The mutated gene is Homeobox gene/Hox gene (e.g., legs instead of antennae in fruit flies)
• Homeotic mutation could result in a new species if the mutation is kept down the germ line
• Drosophila HOX genes


  • Each specifies the function of a segment
  • The HOX genes are arranged on the chromosome in a co-linear fashion
  • The mutants must be due to the shuffling of the gene order, or duplication of specific HOX genes
• Evolution of HOX gene cluster

  • 2 evolutionary genome duplications have given higher organisms 4 HOX clusters - complex bodies
  • All the HOX clusters are working simultaneously to have more complex body plans
  • A change/evolution in the HOX gene leads to a change in the body plan resulting in phenotypic changes (evolve to environmental pressures)
• Embryonic development (humans)


  1. 1st trimester: Early cell divisions, establishment of germ layers ("germinate"), Beginning of organogenesis

  2. 2nd trimester: Organogenesis completes (HOX genes)

  3. 3rd trimester: Foetal growth, functional organ systems, Not changing in structure (b4 6 months)