Embryogenesis and oncogenesis (generation of cancer) share a number of features including cell proliferation, apoptosis, cell migration and invasion, formation of new blood vessels, and differential gene activity. Embryonic cells are relatively undifferentiated, and cancer cells appear to be undifferentiated or dedifferentiated. Homeotic gene expression directs early development, and mutant expression leads to loss of the differentiated state or an alternative cell identity. M. T. Lewis [(2000). Breast Can. Res. 2:158–169] suggested that breast cancer may be caused by the altered expression of homeotic genes. When he examined 11 such genes in cancers, 8 were underexpressed while 3 were overexpressed compared with controls. Given what you know about homeotic genes, could they be involved in oncogenesis?
14. Genetic Control of Development
Developmental Patterning Genes
- Open Question
- Open QuestionWhat phenotypes do you expect in flies homozygous for loss-of-function mutations in the following genes: Krüppel, odd-skipped, hedgehog, and Ultrabithorax?
- Open Question
The specification of the anterior–posterior axis in Drosophila embryos is initially controlled by various gene products that are synthesized and stored in the mature egg following oogenesis. Mutations in these genes result in abnormalities of the axis during embryogenesis. These mutations illustrate maternal effect. How do such mutations vary from those produced by organelle heredity? Devise a set of parallel crosses and expected outcomes involving mutant genes that contrast maternal effect and organelle heredity.
- Open QuestionThe pair-rule gene fushi tarazu is expressed in the seven even-numbered parasegments during Drosophila embryogenesis. In contrast, the segment polarity gene engrailed is expressed in the anterior part of each of the 14 parasegments. Since both genes are active at similar times and places during development, it is possible that the expression of one gene is required for the expression of the other. This can be tested by examining expression of the genes in a mutant background—for example, looking at fushi tarazu expression in an engrailed mutant background, and vice versa.Given the hierarchy of gene action during Drosophila embryogenesis, what might you predict to be the result of these experiments?
- Open QuestionThe pair-rule gene fushi tarazu is expressed in the seven even-numbered parasegments during Drosophila embryogenesis. In contrast, the segment polarity gene engrailed is expressed in the anterior part of each of the 14 parasegments. Since both genes are active at similar times and places during development, it is possible that the expression of one gene is required for the expression of the other. This can be tested by examining expression of the genes in a mutant background—for example, looking at fushi tarazu expression in an engrailed mutant background, and vice versa.Based on your prediction, can you predict the phenotype of the fushi tarazu and engrailed double mutant?
- Open QuestionIn contrast to Drosophila, some insects (e.g., centipedes) have legs on almost every segment posterior to the head. Based on your knowledge of Drosophila, propose a genetic explanation for this phenotype, and describe the expected expression patterns of genes of the Antennapedia and bithorax complexes.
- Open Question
One of the most interesting aspects of early development is the remodeling of the cell cycle from rapid cell divisions, apparently lacking G1 and G2 phases, to slower cell cycles with measurable G1 and G2 phases and checkpoints. During this remodeling, maternal mRNAs that specify cyclins are deadenylated, and zygotic genes are activated to produce cyclins. Audic et al. [(2001). Mol. and Cell. Biol. 21:1662–1671] suggest that deadenylation requires transcription of zygotic genes. Present a diagram that captures the significant features of these findings.
- Open QuestionThe bristles that develop from the epidermis in Drosophila are evenly spaced, so that two bristles never occur immediately adjacent to each other. How might this pattern be established during development?
- Open Question
A number of genes that control expression of Hox genes in Drosophila have been identified. One of these homozygous mutants is extra sex combs, where some of the head and all of the thorax and abdominal segments develop as the last abdominal segment. In other words, all affected segments develop as posterior segments. What does this phenotype tell you about which set of Hox genes is controlled by the extra sex combs gene?
- Open QuestionYou are traveling in the Netherlands and overhear a tulip breeder describe a puzzling event. Tulips normally have two outer whorls of brightly colored petal-like organs, a third whorl of stamens, and an inner (fourth) whorl of carpels. However, the breeder found a recessive mutant in his field in which the outer two whorls were green and sepal-like, whereas the third and fourth whorls both contained carpels. What can you speculate about the nature of the gene that was mutated?
- Open Question
The apterous gene in Drosophila encodes a protein required for wing patterning and growth. It is also known to function in nerve development, fertility, and viability. When human and mouse genes whose protein products closely resemble apterous were used to generate transgenic Drosophila [Rincon-Limas et al. (1999). Proc. Nat. Acad. Sci. (USA) 96:2165–2170], the apterous mutant phenotype was rescued. In addition, the whole-body expression patterns in the transgenic Drosophila were similar to normal apterous.
What do these results indicate about the molecular nature of development? - Open Question
The apterous gene in Drosophila encodes a protein required for wing patterning and growth. It is also known to function in nerve development, fertility, and viability. When human and mouse genes whose protein products closely resemble apterous were used to generate transgenic Drosophila [Rincon-Limas et al. (1999). Proc. Nat. Acad. Sci. (USA) 96:2165–2170], the apterous mutant phenotype was rescued. In addition, the whole-body expression patterns in the transgenic Drosophila were similar to normal apterous.
What is meant by the term rescued in this context? - Open QuestionA powerful approach to identifying genes of a developmental pathway is to screen for mutations that suppress or enhance the phenotype of interest. This approach was undertaken to elucidate the genetic pathway controlling C. elegans vulval development.In a complementary experiment, a gain-of-function let-23 mutant with a multi-vulva phenotype was also mutagenized. What types of mutations will suppress the multi-vulva phenotype?
- Open QuestionA powerful approach to identifying genes of a developmental pathway is to screen for mutations that suppress or enhance the phenotype of interest. This approach was undertaken to elucidate the genetic pathway controlling C. elegans vulval development.A lin-3 loss-of-function mutant with a vulva-less phenotype was mutagenized. Based on your knowledge of the genetic pathway, what types of mutations will suppress the vulva-less phenotype?
- Open Question
In Arabidopsis, flower development is controlled by sets of homeotic genes. How many classes of these genes are there, and what structures are formed by their individual and combined expression?