Development

• Developmental biology is the study of

  1. how a fertilised egg becomes an adult organism
  2. how an adult organism reproduces
  3. how cells and tissue change during an organisms lifetime and how and why organisms age and die
  4. how an adult organism repairs and replaces cells or tissues that have been damaged or injured
• Developmental biology is important as:

  1. ledas to a better understanding of the underlying basis of congenital birth defects
  2. may lead to novel and more effective treatments for human diseases- regenerative medicine
  3. the acquisition of phenotype is a problem- given that selection acts upon phenotype, one cannot truly understand evolution without understanding development
• Parhyale hawaiensis (an amphipod crustacean):

  Advantages:*short generation time

  *genetics*sequenced genome

  *high regenerative capacity

  *transgenesis transparent - imaging
• proto - first deutero - second

  diplo - two triplo - three

  zoa - lifeblast - bud (embryonic / precursor)

  derm - skin (tissue) noto - back

  meso - middle ecto - outside

  meta - after

  chord - string / rope uro - tailcephalo - head

  echino - spiny / prickly

  endo- inside
• Protostome - mouth forms first
• Deuterostome - mouth forms second
• Protozoan - first or primitive life
• Metazoan - multicellular animals
• Diploblastic - containing two tissue layers
• Triploblastic - containing three tissue layers
• Endoderm - tissue (germ layer) on the inside - gives rise to internal organs
• Mesoderm - tissue (germ layer) in the middle - gives rise to notochord, muscle, kidney, blood
• Ectoderm - tissue (germ layer) in the outside - gives rise to skin and nervous system
• Chordate - animals with notochords
• Notochord - “chord in the back”, first tissue to differentiate in chordates
• Urochordate - animals with notochord in their tails
• Cephalochordate - animals with notochords extending into their heads
• Echinoderm - prickly skin - group of animals which include sea urchins
• Developmental processes lead to:

  1. identify conserved mechanisms of development
  2. gain a better understanding of how diversity was achieved during the history of life
  3. better understanding of the causes of congenital diseases
  4. mechanisms that lead to tissue formation, repair and regeneration will lead to novel clinical interventions aimed at improving healing, replacement or regeneration of tissues
• Descriptive embryology - experiments which aim to define normal embryonic development, with minimal disruption of the process. It leads to an understanding of what happens during development, but not how it happens. Descriptive studies are unable to lead to mechanistic insight into how cells achieve their normal fate
• Experimental embryology - experiments which aim to define how embryonic development occurs. For example, how and when do cells acquire their fate. Gain mechanistic insight into how cells gain their fate require experiments that perturb normal developmental processes, and thus require experimental manipulations that alter development
• Morphogenesis - process by which form is generated. Involves coordinated cell movements.
• Gastrulation - morphogenetic process by which the endoderm, mesoderm and ectoderm layers reach their final positions in the embryo.
• Neurulation - morphogenetic process by which the nervous system begins to form, especially formation of the neural tube.
• Blastomere - a cell in the early embryo.
• Fate map - the assessment of the fate of a cell or group of cells based on lineage labelling. It is part of descriptive embryology, as it does not involve disturbing development.
• Specification map - the assessment of what a cell or group of cells will form if removed from their embryonic environment (i.e. removed from their neighbours). It is part of experimental embryology, as it requires that cells or tissues are removed from embryos.
• Determined - a cell or tissue is determined if it will still develop according to its fate, even when transplanted into another site in the embryo - i.e. even when placed in a new environment.
• Competence - the range of cell fates, which can be achieved by a cell or group of cells, given the appropriate conditions. A cell or tissue may be competent to give rise to many cell types that it would not normally be specified or fated to form. 
• Induction - the process by which a cell (or group of cells) emits signals to its neighbouring cells, thereby changing their fate
• The Organizer Experiment 1924

  1.Induction of muscle (somites) and neural tissue

  2. Dorsal mesoderm is determined by the early gastrula stage

  3. Ventral ectoderm and mesoderm arecompetent to become neural and somitic tissue
• Homeotic mutation - mutation which results in the transformation of one body structure into another. Examples: wings instead of halteres; legs instead of antennae; thoracic vertebrae instead of lumbar vertebrae
• Hox gene - family of genes which encode related transcription factors characterised by containing a DNA binding domain, called the homeodomain or homeobox. Evolutionarily conserved.

  *Mutations in this family of genes can lead to homeotic transformations

  *Found clustered in the genome

  *patial and temporal expression shows colinearity, which means that genes in the 3’ end are expressed progressively earlier and more anteriorly than the genes in the 5’ end of the cluster
• How can genes duplicate?

  • Tandem gene duplication (e.g. by unequal cross-over caused by chromosome mis-pairing at meiosis, possibly caused

  by repeat DNA sequences)

  • Segmental duplication (rather like a giant tandem duplication, affecting a whole chunk of a chromosome)

  • Whole genome duplication events

  allotetraploidy = hybridization between two separate species, followed by failure in meiosis

  autotetraploidy = duplication of genome though improper meiosis
• *Two rounds of whole genome duplication events in vertebrate lineage (2R hypothesis)

  *ancesteral cluster

  *duplication event

  *gene loss events

  *2nd round duplication event

  *more gene loss events
• Hox genes expression gives positional identity along the anterior-posterios axis

  Evidence

  1. Expression pattern2. Comparative embryology

  3. Gene knockout experiments
• Hox genes are expressed in distinct proximal-distal patterns

  
• Hox Genes Control Proximal-Distal Identities

  
• Homologous genes = genes that share a common ancestral gene
• Paralogous genes = duplicated genes within a single genome