Chapter 20- Genes and development

1. Chapter 20- Genes and development

2. Where we’re going • An appreciation of what’s involved in producing you from a fertilized egg • Some terms- determination, differentiation, morphogen • Learning a bit about Drosophila early development • Learning a few genes, mutant phenotypes, and what they do.

3. The problem: we’re not just a lump of cells- we differentiate into an individual. • How this happens- the major influences are 1) the DNA- genes involved; and • 2) the signals that the cell(s) receives. 3) the initial structure of the fertilized egg. Thus, IT’S NOT ALL DNA!!!

4. An overview- we have a zygote- fertilized egg; • 1) The zygote is not uniform- there is cytoplasmic localization of components, so that from the start, the cells that result from mitosis are not all the same. (some board work here) • 2) The cells that result send out signals, so there is the cytoplasmic localization, and also the cell-cell interactions. These get VERY,VERY COMPLEX, and eventually result in a new organism.

5. Some terms- • determination- a cell’s fate is set- determined- armpits! • Differentiation- the cell achieves its final form. • We test for determination by transplantation: THOUGHT EXPERIMENT: armpit skin from, say, and 8 year old, transplanted to his belly, would grow armpit hair when he turned 13.- determined before it is differentiated

6. Morphogens • development is often the result of a morphogen- a factor (usually a transcription factor) that is found in a gradient in the cell. The effects of the morphogen depend on its concentration. E.g.- a gradient of a morphogen results in wing production in chickens. This is as if there is a signal coming from the region that is destined to be hand. At high concentrations, it results in a thumb; at lower conc, in an index finger, at still lower a middle finger, etc.

7. The polarizing region produces a gradient of retinoic acid that results in the 4 digits of a chick limb.

8. More weird chicken experiments

9. Salalmanders can regenerate limbs that are cut off. The cut produces a gradient that results in the proper limbs being formed that are distal to the cut. (yeah, embryologists are weird….), Now on to Drosophila development!

10. Next class is a Friday  • That means a quiz  • So stop me at 10:45, and we’ll discuss content. • Developmental Genes- maternal effect genes, hierarchy • Fly development- stages- syncytial blastoderm, cellular blastoderm, • Determination, differentiation, morphogen

11. Cellular blastoderm 512 cells; syncytial blastoderm

12. The “parasegments are shifted ½ segment-

13. Imaginal disks • Some adult parts develop from imaginal disks- Fig. 20-5 These are mostly appendage type structures- eyes, antenna, wings, legs, and genital structures.

14. Imaginal disks- as in “image”

15. II. Developmental genes: • LOTS of studies! • three types of genes, w/ different mutant phenotypes • Fig. 20-4: Maternal effect, and zygotic effect genes; the zygotic effect genes can be further classified as segmentation genes (gap genes, pair-rule genes, and segment polarity genes), and homeotic selector genes. These genes work in a hierarchy- the maternal effect control the Gap, which control the pair-rule and segment polarity, which then control the selector genes. By having these genes work in this manner, you end up with segments- (fig. 20-5).

16. e.g., homeotic selector genes

18. Here is where the concept of a gradient begins to work. We have anterior-posterior asymmetry already established by the maternal effect genes. Thus, the gap genes activated will vary according to the region that a nucleus finds itself in! So, hunchback is activated anteriorly, Kruppel in the middle, and knirps posteriorly. (20-8) Since these all activate different Pair-rule genes, the result is segment-sized pattern differences (20-10)

19. knirps Kruppel Hunchback

20. How transcription factors can form segments.

21. Caption: Stripe pattern of pair-rule gene expression in Drosophila embryo. This embryo is stained to show patterns of expression of the genes even-skipped and fushi-tarazu; (a) low-power view, and (b) high-power view of the same embryo

22. A. Maternal effect genes: • 1. Supplied by the mom • 2. organize the entire body plan. Mutations are catastrophic and lethal- (maintained as heterozygotes) • Bicoid: mutants are an abdomen! Gene product localized in the head region- a determinant for becoming a head! • Oskar: mutants are all head!

23. 1. Gap genes: embryos are missing whole segments. They are responding to the maternal effect gradient, and produce large regions in the embryo. They roughly produce the head, thorax, and abdomen divisions.

24. 2. Pair-rule genes: mutants lack every other segments. fushi tarazu- ftz- not enough segments. gene expressed in every other segment destined to be abdomen • Eve- even skipped- missing the even parasegments.

25. 3. Segment-polarity genes- Dividing the embryo into segments isn’t enough- each segment itself has an anterior and posterior compartment that is distinct. The segment-polarity genes, in response to the gap and pair-rule genes, then proceed to produce anterior and posterior compartments of each segment.

26. C. Homeotic (selector) genes- determine the nature of the segment or parts of it.

27. The most famous example is antennapaedia; This gene is normally expressed in the thorax& abdomen; in the mutants, it is also expressed in the head as well; the addition of this gene activates leg production in the head, and suppresses antenna production. The result is leg growing out of the head. • You can think of this as when the labial genes are on, they produce antennae; but, when antennapaedia is also on, the ant genes override the labial genes, and the same parts go on to produce legs. Other mutations produce extra thorax segments, and even eyes instead of wings.

28. Two interesting things about these genes: • 1) they are expressed in order of their location (20-14);

30. 2) they are highly conserved, and produce segments in mammals as well, which also carry the genes in the order of their expression, although we have more types of selector genes

32. The term HOX gene (homeobox) is used to identify these genes. • Most of the gene products are DNA binding proteins- transcription factors- Some are VERY homologous!! There have been reports of chicken genes replacing fly genes- and they work!

33. What mutants look like • They’re all lethal mutations, except some of the homeotic ones- but they produce embryos that develop partially before dying.

34. Things to know • Terms; examples of how DNA doesn’t rule • Major developmental gene types- maternal and zygotic effect • Major zygotic effect genes and their mutant effects. • They’re transcription factors- Homeodomains

35. Effects of various maternal-effect gene mutation on development. Fig. 21-29, MBOC

36. Fig. 21-36, MBOC