How does a simple cell turn into a complicated organism?
How do genes coordinate and orchestrate the body planning?
Developmental Genetics•how genes control development
Historical Perspectives•Classic developmental genetics (1900-1960)
mutant phenotypes > what gene was and how it worked?•The impact of molecular ideas (1961-1980)
the discovery of mRNA > gene activities are regulated!
•Phenomenon > mechanism•Mutant phenotype > function of WT gene•Development > a program encoded in the genome
Basic approaches:
•Saturation mutagenesisbest example: the Nobel-winning Heidelberg screen
•Clonal analysistrack cell lineage, fate, behavior…
An ideal organism to study development
•Short life cycle (~11 days)•Highly prolific (>100 offsprings / female)•Genetic details established since T.H. Morgan•Relatively small genome (~120Mb, 1/11 of cricket’s)•Only 4 pairs of chromosomes
A Turning Point in the Historyof Developmental Genetics
The October 30, 1980 cover
“Mutations Affecting Segment Number and Polarity in Drosophila”
•Phenomenon > mechanism•Mutant phenotype > function of WT gene•Development > a program encoded in the genome
~150 development-regulating genes that affect gross morphology in Drosophila
stimulated the search for mutant genes affecting development in other systems (nematode and mouse)
virtually all the genes involved in early development of Drosophila are represented also in vertebrates
an amazing conservation of regulatory mechanisms across over 600 million years of evolution
Fluorescence resonance energy transfer Why this is more accurate than single probe detection?
eve gene region
Specific promoter regions of the even-skipped gene control specific transcription bands in the embryo
DorsalizingPhenotype
Rescued by injecting mRNA from WT egg
Early 80’s: 11 maternal effect mutations isolated by Anderson & Nusllein-Volhard
A conserved pathway for regulating nuclear transport of transcription factors in Drosophila and mammals.
Anderson’swork
Based on the previous data obtained by experimental approaches, can we generate a mathematical model to predict the unknown?
1. Can we generate a model that fits current data?
2. If a model fits observation, prediction can be made.
3. Prediction has to be validated by experiments.
A photograph of the snail Oliva porphyria (left), and a computer model of the same snail (right) in which the growth parameters of the shell and its pigmentation pattern were both mathematically generated. (From Meinhardt 1998; computer image courtesy of D. Fowler, P. Prusinkiewicz, and H. Meinhardt.)
A computer simulation based on a Turing reaction-diffusion system
wt pigmentation enzyme mut
(From Asai et al. 1999; photographs courtesy of S. Kondo.)
A computer simulation based on a Turing reaction-diffusion system
Acturalpattern
Coputermodel
Models can only be as good as the data on which it is based, genetic analyses are indispensable for another k years!
Why the haltere doesn’t become another wing?
How is the same morphogen system modulated to generate diver structures?
Dpp made in the wing is able to travel further from AP organizer cells than is Dpp made in the haltere.
Why is that?
1. The Tkv (receptor)-mediated narrowing of the Dpp activity profile (reflected by pMad) in the haltere contributes to the smaller size.
2. Differential levels of Dally
Using dally-lacZ as a reporter,What’s the phenotype of Ubx-/-, en-/-, or antagonizing Dpp signalling?
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