Intro to Developmental Genetics

1
Intro to Developmental Genetics

• By
• Kim Lorenz
• Tom Miller
• Melanie Gasper

2
Model Organisms

• Illuminate many principles applicable to multiple
  species
• Simple, short generation time, easy to cultivate
• Most have sequenced genomes
• And are generally well studied

3
Model Organisms

• Saccharomyces cerevisiae (yeast)
• Complementation analysis
• Arabidopsis thaliana (simple plant)
• Caenorhabditis elegans (nematode)
• Cell lineage
• Drosophila melanogaster (fruit fly)
• Simple developmental pathways
• Mus musculus (mouse)
• Mammalian studies

4
Genetics and Development

• Use mutations to understand developmental
  processes
• Loss of Function
• Gain of Function
• RNAi

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Loss of Function µ

• Null mutations
• No gene product, recessive to normal
• Hypomorphic mutations
• Partial loss of function
• Conditional mutations
• Generally temperature sensitive
• Dominant-negative mutations
• Mutant allele poisons wild-type allele

6
Gain of Function µ

• Excessive gene function
• Result from highly specific changes in the gene
• Ectopic expression
• Expression of gene in abnormal place or time

7
RNA interference

• Cells which ingest dsRNA degrade the
  corresponding mRNA
• No protein synthesis can then occur

8
Mutant Screens

• Saturation mutagenesis and complementation
  analysis
• Suppressor mutations
• Phenotype similar to wildtype
• Enhancer mutations
• 2nd mutation intensifies first mutant phenotype

9
Drosophila notch µ
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Determining Developmental pathways

• Order of Function Analysis
• Arrest development at different stages
• Double Mutant Analysis
• Epistasis
• Gene Interaction Analysis
• How mutations affect gene distribution

11
Determining Gene Regulation

• Embryonic lethal developmental genes are often
  transcription factors
• Post transcriptional control
• mRNA splicing in Drosophila
• C. elegans RNA-blocked translation
• Maternal genes
• Bicoid mRNA

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Asymmetries in development

• Early development is based in asymmetries
• Egg axis
• Stem cells divide asymmetrically

13
Communication is needed for proper development

• Signal transduction pathways
• FGF/FGFR
• Delta/Notch

14
Genes dont explain everything

• cc, the cloned kitten