Sunday, 9 June 2013

Homeobox genes

All vertebrates looks very similar in the early stages of their embryonic development. All animals have the same body plan.

Drosophila melanogaster (fruitfly)

  • The early steps in fruitfly developments are influenced by chemical gradients within the zygote.
  • the gradients are generated by the synthesis of proteins in the eggs before fertilisation
  • this uses information from the maternal effect genes
  • a (bicoid) protein is most intense at the future head end of the fruitfly embryo
    • at this stage, the fruitfly embryo is different from other embryos in that
      • as the zygote divides, no cell membrane form
      • so the nuclei are free in the cytoplasm rather than being contained within distinct cells forming syncytium
      • however, soon the plasma membrane fold inwards around the nuclei in forming single layer of out cells
  • After the initial steps in pattern formation have been taken under the guidance of the gradients, the homeotic genes take over the next more detailed stage (stage of development)
  • homeotic genes that are amazingly similar in structure and function in all animals = genes that direct the building of bodies according to definite body plans
  • homeotic genes code for proteins known as transcription factors which then contol the activity of other genes nearby 
  • all of these genes contain identical sequence of 18 nucleotides called the HOMEOBOX which codes for 60 amino acids
  • the proteins they code for are able to bind with DNa
  • all the genes containing this sequence are called homeoox genes
  • a peculiarity of these is that they are arranged along the chromosomes in the same linear order as the region of the embryo they are controlling
  • since the discovery f Drosophila homeobox genes have been found in many other species incl humans
  • it seems that homeobox genes arose early in evolutionary history and have been guiding embryonic development in animals and plants ever since.
HOX CLUSTERS
  • homeobox genes are arranged in clusters called HOX clusters
  • Nematodes have 1 HOX cluster, Drosophila have 2 HOX clusters and Vertebrates have 4 HOX clusters
  • Increase in number of HOX clusters were probably due to mutations
  • this allowed more complex body plans to develop
  • by controlling the transcription in the cells, homeobox HOX genes act as aster switches determining cell growth and devlopment

Retinpoic acid and birth defects
  • Vitamin A > Retanoic acid > Activates homeobox genes in vertebrates
  • Retanoic acid is a MORPHOGEN - a substance that controls the pattern of development
  • too much Vitamin A in the 1st month of pregnancy interferes with normal expression of genes and can result in birth defect including cranial deformities.

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