Genes and body plans

1. Genes and body plans • The precise sequence of transcription and translation of genes determines the sequence of changes during development • By studying the embryonic development of model animals and plants, researchers have shown howgenes determine the structures produced during development. • In any multicellular organism, development is controlled and coordinated and, more often than not, cells end up where they are meant to be. The development follows a body plan and is under genetic control. • Learning outcome: Explain that the genes that control development of body plans are similar in plants, animals and fungi with reference to homeobox sequences

2. Homeobox genes definition These are genes that control the development of the body plan of organisms, including the polarity (head and tail ends) and the positioning of the organs • These homeobox genes direct development in organisms as diverse as fungi, plants and animals! • Homeobox genes each contain a sequence of 180 base pairs=homeobox • This sequence produces polypeptides of about 60 amino acids • Some of these are transcription factors and regulate gene expression of other genes • And so the control of development/body plans • Homeobox genes in animals are arranged in clusters known as Hox clusters

3. Homeobox genes • What structures develop where is controlled by ‘master genes’ (called homeoboxgenes). • The master genesproduce mRNA • This is translated into ‘signal proteins’ • Which switch on other genes • (i.e. mRNA produced, resulting in the synthesis of proteins) • Responsible for producing the proteins needed for the specialisation of cells in each segment to produce the different structures

4. Development of Drosophila • The following outline shows how they are important in controlling the body plan of fruit fly.

5. Eggs laid and mitotic divisions occur at rate of 1 every 6-10 minutes • No new cell membranes initially=multinucleate mass • 8th division: the 256 nuclei migrate to outer section • By 11th division these =outer layer around yolk filled core • Division rate slows and genes start transcribing • Plasma membrane folds inwards • 2-3 hours later the embryo divides into a series of segments which correspond to the body plan

6. The fruit fly has the body plan of a typical insect, i.e. the adult has a segmented body with a head section, a thorax (three segments T1, T2 and T3) and an abdomen. Each of the thorax sections has a pair of legs; there is a pair of wings on T2 and a pair of balance organs on T3. • Homeobox genes control the polarity of the body, polarity of the segments and the development of individual segments.

7. Development in insects Types of Homeobox genes • Maternal-effect genes: Polarity genes (head: anterior; tail posterior) • Segmentation genes: polarity of each segment • Homeotic selector genes: specify the identity of each segment and direct the development of individual body segments. • These are the master genes and consist of 2 gene families: one that regulates the development of the thorax and abdomen, and that regulates the head and thorax

8. Mutations of these genes can occur: For example in the head the homeobox genes produce signal proteins that switch on the genes that result in the development of antennae http://www.dnalc.org/view/16760-Animation-37-Master-genes-control-basic-body-plans.html

9. However a mutation of the gene can result in the production of a different signal protein that switches on different genes. In this example, instead of antennae, legs are produced instead on the head!

10. Watch • What does this tell us? • http://www.youtube.com/watch?v=LFG-aLidT8s

11. Homeobox genes • Most animals have very similar homeobox genes. • They are general purpose in the sense that they are similar in many organisms; it doesn’t matter if it’s a mouse’s head or a fly’s head that is being built, the same gene directs the process. • Small changes in such powerful regulatory genes, or changes in the genes turned on by them, could represent a major source of evolutionary change • Genes are highly conserved (have not evolved much) because they are very important genes • Mutation would have a big effect on body plans/development of organisms • It would affect many other genes • As a result mutation could be lethal or selected against • http://learn.genetics.utah.edu/content/variation/hoxgenes/ Good extension reading

12. Expression of Homeobox genes • Homeobox genes are expressed in specific patterns in certain stages of development of embryo in vertebrates and invertebrates • They specify the identity and fates of the embryonic cells and development of the body plan. • They are activated in the same order as they are expressed along the body from the head (anterior) to the tail (posterior) • https://www.youtube.com/watch?v=drS4u8cO2bE 3.20

13. THINK? • Suggest why the Hox genes are found in clusters • This indicates it is important for the genes to be linked and inherited together as a unit • It would reduce disruption by crossing over and recombination.

14. Homeobox genes • Thalidomide disrupted the Homeobox genes in developing foetuses, so arms and legs did not develop properly. • In humans Hox A11 and Hox D11 switch on the genes for development of the forelimb. It has been suggested that thalidomide may have switched off the homeobox genes for limb development and so caused the birth defects typical of thalidomide use. Thalidomide can certainly insert itself into DNA and inhibits production of new blood vessels in limb buds.

15. Other factors • Affecting the pattern of tissue development • Read the article • Highlight the key points to summarise

16. Vitamin A is involved in immune function, vision, reproduction, and cellular communication Vitamin A is critical for vision as an essential component of rhodopsin, a protein that absorbs light in the retinal receptors, and because it supports the normal differentiation and functioning of the conjunctival membranes and cornea. Vitamin A also supports cell growth and differentiation, playing a critical role in the normal formation and maintenance of the heart, lungs, kidneys, and other organs 

17. Retinoic acid • Derivative of Vitamin A • Can activate homeobox genes in vertebrates in same order as they are expressed • It is a natural morphogen: a substance that governs the pattern of tissue development • Too much Vitamin A taken during early pregnancy can interfere with normal expression • Leads to birth defects: cranial/limb deformities