Genetic Model Organisms

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Genetic Model Organisms
mouse
worm
fish
yeast
fruit fly
weed
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Drosophila melanogaster Genetics and
Developmental Biology Physiology and Behavior
Many disease-causing genes in humans have
corresponding homologues in the fly
genome Cancer Neurodegenerative
disease Drug addictions Diabetes Obesity
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Life cycle of Drosophila

• embryogenesis
• three larval stages
• a pupal stage
• the adult stage

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Groups of cells called imaginal discs are set
aside at specific sites in the larval body.
From these the various body parts develop
during pupation (adult muscle, the nervous
system, etc).
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Advantages of the fly system

• A relatively short life cycle (10 days)
• Culturing flies is cost-effective (vs mice)
• A variety of genetic and molecular tools
  available (functional testing in vivo)
• Complete genome sequence (13,500 genes)

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Advantages of the fly system

• A relatively short life cycle (10 days)
• Culturing flies is cost-effective (vs mice)
• A variety of genetic and molecular tools
  available (functional testing in vivo)
• Complete genome sequence (13,500 genes)

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Thomas H. Morgan and the Caltech fly group

• Bridges (left) and Sturtevant in 1920 
• (B) Morgan in 1917

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Christiane Nüsslein-Volhard, Eric Wieschaus and
the Baden fly group
(1980)
Nüsslein-Volhard and Wieschaus (along with Edward
Lewis) were awarded the 1995 Nobel Prize for
Physiology/Medicine.
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Saturation Mutagenesis Screen and the
Segmentation Hierarchy
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Biological question Screening assay Speed Speci
ficity Lead to biological insight?

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Time table of embryogenesis
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Drosophila embryogenesis
3 h
pole cells (germ line)
Cellular blastoderm
Anterior
Posterior
10 h
Segmented embryo
22 h
1st instar larva
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Mutant bicoid embryo
a
b
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Mutations insegmentation genes
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Segmentation Hierarchy
Maternal genes Gap genes Pair rule
genes Segment polarity genes

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Molecular Cloning of Genes
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Molecular Mechanisms

What is the gene product? Where and when is it
active? Was the genetic prediction correct?
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Segmentation fate map of Drosophila embryo
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Drosophila early development
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ftz (fushi tarazu) gene expression pattern

in situ hybridization (RNA detection) need probe!
Ernst Hafen and Walter Gehring (1983)
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even-skipped (blue), ftz (red)
antibody staining (protein detection) need
antibody!
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Gap Genes
hunchback (blue) and Krueppel (green)
Fluorescent staining
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Molecular patterningof the embryo
Bicoid (blue) Even skipped (red) Krüppel
(yellow)
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Segmentation Hierarchy
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Biological question Screening assay Speed Speci
ficity Lead to biological insight?

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Germ-line Transformation and in vivo Genetic
Manipulations
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For example...
Is the striped expression of ftz really
necessary? What happens if you express ftz
everywhere? How would you test this?
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Heat shock promoter-ftz P-element plasmid
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ftz
Adapted from Wang and Lin, 2004
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Syncitial blastoderm
Germ cells
Transposable P-element mediated transformation
Allan Spradling and Gerald Rubin (1982)
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Drosophila embryogenesis
3 h
pole cells (germ line)
Cellular blastoderm
Anterior
Posterior
10 h
Segmented embryo
22 h
1st instar larva
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(No Transcript)
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The UAS-Gal4 System How you can make flies with
eyes on their legs
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Regulating Gene Activity with Pinpoint Precision
progeny flies will express gene in the place of
choice
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wild-type
Misexpression of eyeless using the UAS-Gal4 system
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wildtype
obese (leptin)