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The problem of development. Eörs Szathmáry (Alpbach 2005). Collegium Budapest. Eötvös University Budapest. What’s this?. Let’s take another look!. Aggregation of the slime mold. The amoebae gather into a focus Individual cells become bipolar. Propagation of the cAMP signal and chemotaxis.
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The problem of development Eörs Szathmáry (Alpbach 2005) Collegium Budapest Eötvös University Budapest
Aggregation of the slime mold • The amoebae gather into a focus • Individual cells become bipolar
Propagation of the cAMP signal and chemotaxis • Central cell emits a dose of cAMP then it rests for a while • Neighbouring cells creep toward the signal while they also release a dose of cAMP
Formation of Dictyostelium fruiting body • In the slug pre-stalk cells are first • Finally pre-spore cells creep to the front
Why is the problem of development so difficult? • We do not build developing machines: physiology is „easy”, embryology is „difficult”
Preformation versus epigenesis • Homonculus in the sperm • Epigenetics: complexity truly increases
Self-assembly of the virus capsid • Subunits are composed of proteins
Do the genes programme ontogenesis? • In a sense yes, BUT • A bag of elephant proteins is not an elephant • Structure that self-assemble • Virus particles • The formation of sponges • Limitations of the jigsaw puzzle principle
Wave-like properties of development • Wave forms are largely independent of chemical composition • Animal coat patterns (zebra, tiger, etc.) • BUT altered genes can alter the shape of the elephant • Somehow molecules determine form even if they do not self-assemble • BUT HOW?
The lesser know work of Alan Turing • English mathematician • Breaking of the german code • Creator of the „universal Turing machine” • His relevant paper: Philosophical Transactions of the Royal Society (1952) • What is behind animal coat patterns?
Theory of a chemical standing wave • Two compounds: an activator and an inhibitor • The activator helps its own formation • Inhibitor inhibits the formation of the activator • Both compounds degrade • Inhibitor diffuses much faster
A kémiai állóhullám • In a well-stirred medium both concentrations reach equilibrium • If the solution is not stirred, then a positive fluctuation in activator concentration will enhance itself • Fluctuation is due to chance • Inhibitor concentration also rises, but its higher diffusion rate decrease the amplitude
The coat of a fish • Growth as well as REGENARATION seems to follow a Turing mechanism • Reaction-diffusion systems
Wolpert: a „French flag” A simple model of pattern formation
Positional information and pattern formation • Each person has a specific seat in the stadium • In each seat a specific poster must be shown
Hair patterns in Oncopeltus as indicator of polarity • Hairs point backwards on the cuticule • Removal of segment boundary reverses the direction of hair growth
Development of the chick limb • The zone of polarizing activity (ZPA) directs the formation of the order of digits
Prepattern and consequence • Morphogen is the sonic hedgehog protein
The expression of maternal bicoid mRNA • Both mRNA and protein can be visualized by appropriate compounds
Determination of the 2nd even-skipped (eve) stripe • Bicoid and hunchback proteins activate • Giant and Krüppel inhibit • Not too elegant!
Gene expression and pattern • Combinatorial determination
Vizsgaidőpontok • Január 7, 14, 21, 28 KEDDEK, Szabó József terem 10-12 óra • Január 9, 16, 23 CSÜTÖRTÖKÖK, Szabó József terem