1. Homeobox Genes
Body organisation

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

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

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.

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
Mutant with legs growing out of head
Normal

6. Antennapedia complex (group of Homeobox genes)
5 genes that affect the anterior part of the fly
When mutated, legs grow instead of antennae

7. Bithorax gene complex (3 homeobox genes affecting thoracic development)
Normal – wings on 2nd thoracic segment and 2 halteres on 3rd thoracic segment (far left photo, halteres in white)
Mutant – 3rd segment has wings so 2 sets of wings and no halteres

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

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

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.

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.

12. Hox genes
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
Hox genes are known to control body development
General trend for simpler animals to have fewer Hox genes and Hox gene clusters
Comparison of Hox gene evolution and animal evolution bear striking parallel

13. Hox genes 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

14. Hox genes in the Animal Kingdom

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

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

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

18. Gastrulation involves cells migrating to the interior
3 cell layers formed- ectoderm, mesoderm and endoderm
Segmented body plan develops
Head, thorax and abdomen, segmentation established
Larva – free living
Pupa – undergoes metamorphosis
Adult
Egg to adult in 10 days

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
Follow colinearity rule
Key role in patterning anteroposterior axis

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

21. Four general phases for body formation
Organize body along major axes
Organize into smaller regions (organs, legs)
Cells organize to produce body parts
Cells themselves change morphologies and become differentiated

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.

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
Cell division,
cell migration,
cell differentiation or
cell death (apoptosis)

25. Position or Spatial Organization is Everything
2 main mechanisms used to communicate positional information
Morphogens
Cell adhesion

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