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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 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 The process of aggregation Formation of the anteroposterior axis of Drosophila 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 The effect of ZPA Prepattern and consequence Morphogen is the sonic hedgehog protein Again the axis of Drosophila The expression of maternal bicoid mRNA Both mRNA and protein can be visualized by appropriate compounds Determination of the 2nd evenskipped (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