The problem of development Collegium BudapestEötvös University Budapest Eörs Szathmáry (Alpbach 2005)

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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” 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 antero- posterior axis of Drosophila

Do the genes programme ontogenesis? In a sense yes, BUT In a sense yes, BUT A bag of elephant proteins is not an elephant A bag of elephant proteins is not an elephant Structure that self-assemble Structure that self-assemble  Virus particles  The formation of sponges Limitations of the jigsaw puzzle principle Limitations of the jigsaw puzzle principle

Wave-like properties of development Wave forms are largely independent of chemical composition Wave forms are largely independent of chemical composition Animal coat patterns (zebra, tiger, etc.) Animal coat patterns (zebra, tiger, etc.) BUT altered genes can alter the shape of the elephant BUT altered genes can alter the shape of the elephant Somehow molecules determine form even if they do not self-assemble Somehow molecules determine form even if they do not self-assemble BUT HOW? 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 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 óra Január 7, 14, 21, 28 KEDDEK, Szabó József terem óra Január 9, 16, 23 CSÜTÖRTÖKÖK, Szabó József terem Január 9, 16, 23 CSÜTÖRTÖKÖK, Szabó József terem