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Homeobox Genes Body organisation Slide 2 Cell Differentiation Cell differentiation is the development of non-specialised cells into cells with specialised functions. Examples: muscle cells, liver cell, red blood cells As organisms grow and develop from fertilised eggs; organs and tissues develop to produce a characteristic form. The process is called morphogenesis. Both processes are controlled by gene expression Slide 3 What is gene expression? Gene expression is the activation of a gene that results in a polypeptide or protein. The expression of some genes results in the production of a protein that can turn on or switch off other genes. Transcription factors Slide 4 Body plans Every organism has a unique body pattern because of the influence of HOMEOBOX genes. These specify how different areas of the body develop their individual structures, eg. Arms, legs etc Homeobox genes were discovered when geneticists studying fruit flies found mutants with legs growing where their antennae should be and 2 sets of wings instead of 1. Slide 5 Homeotic Genes Homeotic genes are regulatory genes that determine where certain anatomical structures, such as appendages, will develop in an organism during morphogenesis. These seem to be the master genes of development Normal Mutant with legs growing out of head Slide 6 Antennapedia complex (group of Homeobox genes) 5 genes that affect the anterior part of the fly When mutated, legs grow instead of antennae Slide 7 7 Bithorax gene complex (3 homeobox genes affecting thoracic development) a.Normal wings on 2 nd thoracic segment and 2 halteres on 3 rd thoracic segment (far left photo, halteres in white) b.Mutant 3 rd segment has wings so 2 sets of wings and no halteres Slide 8 Homeotic genes encode homeotic proteins that function as transcription factors which switch on other genes The Homeobox is a coding sequence within homeotic genes which contains 180 base-pair sequences, codes for 60 amino acid polypeptide Encodes homeodomain for DNA binding Slide 9 Homeobox In Drosophila (fruit flies) the specific DNA sequence within a homeotic gene that regulates patterns of development is the homeobox. The same or very similar homeobox sequences have been found in many other eukaryotic organisms Slide 10 Homeobox (HOX genes) The HOX genes encode important transcription factors. These specify cell fate and identify the embryonic pattern along the primary axis (anterior/posterior) As well as the secondary axis (genital and limb bud) Major role Development of CNS, axial skeleton, positioning of limbs as well as the gastrointestinal and urogenital tract. Homeotic genes involved in spatial pattern control and development contain a conserved 180-bp sequence known as homeobox. This encodes a 60-amino- acid domain that binds to DNA. The Hox proteins regulate other executive genes that encode transcription factors or morphogen signals, as well as operating at many other levels, on genes that mediate cell adhesion, cell division rates, cell death and cell movement. In Humans as in most vertebrates there are 4 homeobox gene clusters (39 HOX genes), located on chromosomes 7p14, 17q21,12q13 and 7q31. Drosophila has eight Hox genes arranged in a single cluster on a single chromosome. Slide 11 A. Drosophila's eight Hox genes in a single cluster and 39 HOX genes in humans. B. Expression patterns of Hox and HOX genes along the anterior-posterior axis in invertebrates and vertebrates. Slide 12 Three lines of evidence support the idea that Hox gene complexity has been instrumental in the evolution and speciation of animals with different body patterns 1.Hox genes are known to control body development 2.General trend for simpler animals to have fewer Hox genes and Hox gene clusters 3.Comparison of Hox gene evolution and animal evolution bear striking parallel Hox genes Slide 13 Found in all animals Genetic variation may have been critical event in the formation of new body plans Number and arrangement of Hox genes varies among different types of animals Increases in the number of Hox genes may have led to greater complexity in body structure Slide 14 Hox genes in the Animal Kingdom Slide 15 Fruit flies have only one Antennepedia-bithorax complex Humans and many other vertebrates have 4 similar Hox gene clusters They probably arose through gene duplication Hox genes shape the number and appearance of body segments (repeated structures) along the main body axes of both vertebrates and invertebrates Slide 16 How is a multicellular organism made? Polarity Even before fertilisation an egg has a gradient of proteins that help to establish its polarity (which end becomes the head or anterior and which is the tail, posterior) After fertilisation Maternal Effect genes reinforce this polarity and also establish the dorsal (back) and ventral (belly) orientation Polarity is the formation of the axis by which the embryo differentiates Once the orientation is in place other genes are switched on Segmentation occurs driven by Gap genes, Pair rule Genes and Segmentation genes Finally the Homeotic Selector genes are switched on These control the final specialised development of each segment See Page 114 Text book Slide 17 Animal development Drosophila model Fertilised egg establishes the pattern for the adult body plan Elongated cell with positional information After fertilization, zygote develops into blastoderm Series of nuclear divisions without cytoplasmic division (produces many free nuclei) synctial blastoderm Individual cells are created after nuclei line up along cell membrane (cellular blastoderm) See page 114 Slide 18 3.Gastrulation involves cells migrating to the interior 3 cell layers formed- ectoderm, mesoderm and endoderm 4.Segmented body plan develops Head, thorax and abdomen, segmentation established 5.Larva free living 6.Pupa undergoes metamorphosis 7.Adult 8.Egg to adult in 10 days Slide 19 A Homologous Group of Homeotic Genes Is Found in All Animals Vertebrate Hox genes are homologous to those that control development in simpler organisms such as Drosophila Homologous genes are evolutionarily derived from the same ancestral gene and have similar DNA sequences Hox genes in mice 1.Follow colinearity rule 2.Key role in patterning anteroposterior axis Slide 20 Homeotic genes in Mus The mouse has Hox genes on 4 different chromosomes Hox genes are similar to those found in invertebrates but spread across more chromosomes Slide 21 Four general phases for body formation 1.Organize body along major axes 2.Organize into smaller regions (organs, legs) 3.Cells organize to produce body parts 4.Cells themselves change morphologies and become differentiated Slide 22 Hox genes determine the number and types of vertebrae in animals Hoxc-6 determines that in the chicken the 7 vertebrae will develop into ribs Snake: Hoxc-6 is expanded dramatically toward the head and toward the rear so all these vertebrae develop ribs. Slide 23 Positional information during development Each cell in the body must become the appropriate cell type based on its relative position. Each cell receives positional information that tells it where to go and what to become. Cells may respond by 1.Cell division, 2.cell migration, 3.cell differentiation or 4.cell death (apoptosis) Slide 24 Slide 25 Position or Spatial Organization is Everything 2 main mechanisms used to communicate positional information 1.Morphogens 2.Cell adhesion Slide 26 Cell adhesion Each cell makes its own cell adhesion molecules (CAMs) Positioning of a cell within a multicellular organism is strongly influenced by the combination of contacts it makes with other cells and with the extracellular matrix