L20: Pattern Formation of Drosophila

Question 1

what are the two differences in early embryo patterning mechanisms?

Answer 1

1. egg fertilization - egg polarity (fly egg is highly polar where as a mouse/human egg is nonpolar)
2. Early embryo - most animals go through cleavage divsions but the fly goes through syncytium

Question 2

why do we care about Drosophila development?

Answer 2

-short generation time - 9 days to sexual maturity
-sophisticated genetic and molecular biology tools
-studies in drosophila have revealed how genetic control mechanisms govern development
-many basic mechanisms, including the functions of specific molecules (Hox genes), are conserved in humans

Question 3

fate map of fly development

Answer 3

questions:
* How does this segmented pattern forms?
* How does each segment know its identity?
* How is the pattern maintained throughout development?

approach: genetic screens (looking for mutants with defects)

Question 4

drosophila early embryo is a syncytium

Answer 4

1. unfertilized fly egg is already polarized
2. fertilized egg
3. many nuclei divide rapidly in a syncytium
4. nuclei migrate to periphery, where cell boundaries will eventually form
5. 13 divisions prior to cellularization, forms multiple somatic cells

Question 5

bristle patterns reveal…

Answer 5

distinct anterior-posterior (A-P) difference among and within segments

Question 6

egg-polarity gene (bicoid)

Answer 6

missing anterior or posterior segments

Question 7

what are the three segmentation genes?

Answer 7

1. gap gene - missing several contiguous segments
2. pair-rule gene - missing alternating segments
3. segment-polarity gene - polarity defect in every segment

Question 8

hierarchy of gene regulatory interaction patterns

Answer 8

first, egg polarity genes organize the A-P axis of early embryo (prior to fertilization)

this affects expression of three groups of genes which control segmentation along A-P axis: gapm pair-rule, seegment-polarity genes

Question 9

hox genes…

Answer 9

give identity to each segment

Question 10

egg polarity genes…

Answer 10

encode maternal molecules deposited in the egg

bicoid mutants lack anterior
segments

• Maternal bicoid mRNA is localized
  to the anterior of the egg prior to
  fertilization
• Bicoid protein is made after
  fertilization and diffuses in the
  syncytium, forming a gradient
  from anterior to posterior
• Bicoid is a transcription regulator
• Bicoid regulates the expression of
  gap and pair-rule genes
• Bicoid acts as a morphogen!
  Activates expression of genes in a
  concentration-dependent manne

Question 11

egg-polarity gene products form opposing gradients

Answer 11

Question 12

egg polarity gene product gradients induce epression of zygotic genes and turn on —– genes

Answer 12

GAP genes

Question 13

gap genes are…

Answer 13

• Expressed in broad domains (multiple segments)
• Encode transcription regulators
• Their expression is regulated by
  egg-polarity genes
• They regulate the expression of
  other gap genes and pair-rule genes

Question 14

pair-rule genes…

Answer 14

• Mutants lack every other segment
  (either odd or even segments
  depending on the gene)
• Expressed in 7 segments (either
  even or odd) ~ or 7 ‘stripes’
• Encode transcription factors
• Their expression is regulated by
  gap genes and egg-polarity genes
• They regulate the expression of
  other pair-rule genes and
  segment-polarity genes

Question 15

how to determine which factors regulate the expression of a gene?

Answer 15

example: Gene A

Question 17

pair rule genes….

Answer 17

*Mutants lack every other segment
(either odd or even segments
depending on the gene)

• Expressed in 7 segments (either
  even or odd)
• Encode transcription factors
• Their expression is regulated by
  gap genes and egg-polarity genes
• They regulate the expression of
  other pair-rule genes and
  segment-polarity gene

Question 18

how do segment polarity genes differ from the other three types of genes?

Answer 18

they maintain their expression through development

encode transcription factors and signaling pathway components

other three gene types remain inmemory of cells but do not remain expressed, only transiently expressed

Question 19

a signaling loop maintains expression of segment polarity genes

Answer 19

Engrailed, Wingless and Hedgehog, are segment polarity genes expressed at posterior end of each
segment in neighboring cells

• Engrailed = transcription factor; Wingless and Hedgehog are secreted proteins and paracrine
  signaling molecules
• MUTUALLY REINFORCING SIGNALS between Wingless expressing cells and Hedgehog expressing
  cells maintains the narrow stripes of expression (cell memory) throughout development

Question 20

when are each type of gene expressed in terms of the fly cell cycle of development

Answer 20

Question 21

how do the segments know their identity (i.e. what they should become?)

Answer 21

hox genes

Question 24

expression pattern and function of Hox proteins

Answer 24

Hox proteins are….
-transcription regulators that bind to DNAA through their homeodomains
-act as master regulators by controlling the expression of multiple genes

Question 28

hox gene is maintained in adults, occurs via…

Answer 28

Hox gene expression must be maintained
throughout development

This occurs via epigenetic inheritance of
histone modifications & recruitment of
chromatin remodeling complexes

The Hox genes are present and play a role in
anterior-posterior patterning in all bilaterally
symmetric animals, including vertebrates

first molecular evidence that development of all animals was based on common principles and molecular mechanisms

Question 28

Hox genes regulate limb development in vertebrates

Answer 28

mutations of different Hox genes will result in malformations of specific regions of the limb (S, Z, A regions)

Question 28

what are paralogs

Answer 28

similar gene sequences that have similar expression patterns