Genetics #11

Two clusters of homeotic genes work together to specify body segment identity during Drosophila development. Expression of these gene products is described as being within parasegments. (Note: The term "segment" refers to each outwardly observable and distinct body section, whereas "parasegment" refers to regions of gene expression.)

1. In Drosophila, the homeotic genes act in combination to specify the identity of the 14 body segments. Two clusters of homeotic genes have been found on chromosome 3: the Antennapedia complex consists of five genes, and the bithorax complex consists of three genes. 2. All eight homeotic genes encode closely related proteins that share a conserved sequence of 180 nucleotides of DNA called the homeobox, which codes for a 60-amino acid protein domain called the homeodomain. 3. Analyses have determined that these homeobox genes share molecular and functional similarities, as well as a common evolutionary origin. The combination of these properties has resulted in them collectively being called Hox genes.

You are a graduate student in the lab of a famous fly geneticist. You need to analyze a batch of mutant flies that were recently created in her laboratory to identify the single gene that is most likely mutated in each of the flies.

1. Mutant fly X has lost the head and thorax. The gene most likely responsible for this mutation is hunchback (a gap gene). 2. Mutant fly F has predominantly lost abdominal structures, which is likely the result of a mutation in knirps (a gap gene). 3. Segment-sized sections of every other segment are missing in mutant fly Z. One likely candidate gene is even-skipped (a pair-rule gene). 4. The mutation observed in mutant fly O resulted in defects within the anterior or posterior regions of each segment. The gene that most likely caused this mutation is hedgehog (a segment-polarity gene). 5. The wings are missing in mutant fly L, which is likely the result of a mutation in wingless (a segment-polarity gene). 6. Thoracic and abdominal structures are missing in mutant fly Q. The gene most likely responsible for this mutation is Kruppel (a gap gene).

Two different sets of genes control embryonic development in Drosophila: maternal-effec genes and zygotic genes. Products of the maternal-effect genes (mRNA and/or proteins) are distributed in a gradient throughout the egg and regulate the expression of the first three groups of zygotic genes (gap, pair-rule and segment polarity genes). Which model most accurately describes how maternal-effect genes regulate embryonic development in Drosophila?

A. Embryonic development is initiated by molecular gradients of maternal effect gene products throughout the embryo. These gene products activate or repress the expression of zygotic genes in both a temporal and spatial manner B. Embryonic development is initiated by maternal effect gene products confined to the anterior end of embryo. These gene products set off a cascade of activation of zygotic genes starting at the anterior end moving toward the posterior end. C. Embryonic development is initiated by maternal effect genes that activate zygotic genes within the anterior end of the embryo and repress zygotic genes within the posterior end of the embryo. D. Embryonic development is initiated by maternal effect gene products confined to the posterior end of the embryo. These gene products set off a cascade of activation of zygotic genes starting at the posterior end moving toward the anterior end.

B. Classify each phrase or term as applying to fly A only, fly B only, or both fly A and fly B. The term "Hox genes" applies to clusters of homeotic genes found in many different animals, including fruit flies. After segmentation genes have established the body segments, Hox genes trigger the development of segment-specific body structures in the correct locations. For more on Hox genes, see Hints 2 and 3.

B. Fly A ONLY: "wild type," "possesses normal Hox genes," "exhibits normal pattern formation" Fly B ONLY: "exhibits abnormal pattern formation," "homeotic mutant," "possesses mutant Hox genes' Both Fly A and Fly B: "produces transcription factors triggering gene expression for segment-specific structures"

The regulation of gene expression in individual cells coordinates the development of multicellular organisms, ensuring that tissues and organs form in their characteristic places. Researchers can study how multicellular organisms develop their spatial organization by examining normal and mutant forms of organisms, such as the fruit fly, Drosophila. Which of the following statements about pattern formation are true?

Differential gene expression affects the developmental process in animals. Positional information controls pattern formation. Cells receive molecular signals that communicate their position in relation to other cells. Homeotic genes code for transcription factors that control the development of segment-specific body parts.

Which model most accurately describes how maternal-effect genes regulate embryonic development in Drosophila?

Embryonic development is initiated by molecular gradients of maternal effect gene products throughout the embryo. These gene products activate or repress the expression of zygotic genes in both a temporal and spatial manner. Maternal-effect genes encode transcription factors and proteins that regulate zygotic gene expression during embryonic development. The maternal effect gene products control the activation or repression of the expression of zygotic genes in both time and space throughout embryonic development.

Which model most accurately describes how Hox genes regulate embryonic development in Drosophila?

Hox gene expression marks the boundaries of parasegments. Each parasegment expresses a unique combination of Hox gene products that give rise to the identity of each parasegment.

How would hunchbackhunchback expression be altered?

Hunchback expression would be increased.

Given that maternal bicoidbicoid activates the expression of hunchbackhunchback (see the figure below), what would be the consequence of adding extra copies of the bicoidbicoid gene by transgenic means, thus creating a female fly with two (the wild-type condition), three, or four copies of the bicoidbicoid gene?

Increased dosage of the bicoidbicoid gene will result in an increase in the amount of bicoidbicoid mRNAmRNA and therefore bicoidbicoid protein.

What about the expression of other gap genes and pair-rule genes?

The altered gradient of bicoid protein in the egg alter the expression of genes downstream of bicoid function.

This pedigree shows the inheritance pattern of a recessive maternal effect gene in Drosophila. In maternal effect, the offspring's phenotype is under the control of nuclear gene products present in the mother's egg. In this example, the presence of the a + allele in the mother is required for proper wing development in the offspring. In the pedigree, individuals who are wingless are indicated by a shaded symbol. The phenotypes and genotypes are only provided for the first generation (individuals 1 and 2). Pedigree showing 3 individuals: Individual 1 (mother) has wild-type wing phenotype and genotye a/a; individual 2 (father) has wingless phenotype and genotype a+/a; their daughter's phenotype and genotype are unknown.

a +/a a/a For a maternal effect trait, an offspring's genotype is determined by independent assortment of the alleles from both parents. The offspring indicated by the "?" could either get an a allele from both parents or an a from the mother (individual 1) and an a + from the father (individual 2). Therefore her possible genotypes are a +/a or a/a.

What would be the consequence of ectopically expressing Hoxd11 throughout the developing mouse limb bud?

converting the index finger into a middle finger.

What would be the consequence of ectopically expressing Hoxd10 and Hoxd11 throughout the developing mouse limb bud?

converting the thumb into a middle finger. converting the index finger into a middle finger

What would be the consequence of ectopically expressing Hoxd10 throughout the developing mouse limb bud?

converting the thumb into an index finger.

Certain mutations in non-Hox genes actually produce homeotic mutants due to a failure to modulate chromatin acetylation appropriately. What is this influence on cellular "memory" called?

epigenetic

A 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?

gain-of-function lin-3 receptor mutants gain-of-function intracellular signal molecule (LET-60) activated by lin-3 mutants

A mutation in a fly causes an antenna to develop where a leg should be. This is an example of a ________ mutation.

homeotic

What term describes the process by which a cell acquires a certain fate from its neighboring cell?

induction

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?

loss-of-function lin-3 receptor mutants loss-of-function intracellular signal molecule (LET-60) activated by lin-3 mutants

What substance, in different concentrations, directs developmental fates?

morphogen

What about if the anchor cell is ablated in a let-23 gain-of-function mutant?

multi-vulvate

the hunchback protein occurs along a gradient, where the anterior embryo has high protein levels and the posterior has low levels, yet the hunchback mRNA is found at the same concentration throughout the embryo. These observations suggest that hunchback must be regulated ________.

posttranscriptionally

There is much controversy in the news-both scientific and popular-about the use of embryonic stem cells for research. These cells are grown as cell lines in culture, created by taking the inner cell mass from 5-day-old embryos. What is the center of the controversy?

the difference of opinion about whether these embryos are persons

Human Hox genes are in four clusters: HOXA, HOXB, HOXC, and HOXD, for a total of 39 genes. Besides conserving the clustering of genes, evolution has also conserved ________.

the order of the genes within the clusters

Ablation of the anchor cell in wild-type CC. elegans results in a vulva-less phenotype. What phenotype(s) is to be expected if the anchor cell is ablated in a let-23 loss-of-function mutant?

vulva-less

What is the phenotype of the female indicated by the "?" in the pedigree?

wingless For a maternal effect trait, the phenotype of all offspring is determined by the genotype of the mother. The mother deposits gene products into the embryo, and these gene products are used by the embryo before it starts making its own gene products. In this case the mother is a/a so she cannot produce any normal gene products for this trait; therefore all of her offspring will be mutant (wingless).