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

The problem of development

Collegium Budapest Eötvös University Budapest

Eörs Szathmáry (Alpbach 2005)

What’s this?

Let’s take another look!

Aggregation of the slime mold

The amoebae gather into a focusThe amoebae gather into a focus Individual cells become bipolarIndividual cells become bipolar

Propagation of the cAMP signal and chemotaxis

Central cell emits a Central cell emits a dose of cAMP then it dose of cAMP then it rests for a whilerests for a while

Neighbouring cells Neighbouring cells creep toward the creep toward the signal while they also signal while they also release a dose of release a dose of cAMPcAMP

Formation of Dictyostelium fruiting body

In the slug pre-stalk In the slug pre-stalk cells are firstcells are first

Finally pre-spore cells Finally pre-spore cells creep to the frontcreep to the front

SORTing.MOV

Why is the problem of development so difficult?

We do not build developing machines: We do not build developing machines: physiology is „easy”, embryology is physiology is „easy”, embryology is „difficult”„difficult”

Preformation versus epigenesis

HomonculusHomonculus in the in the spermsperm

Epigenetics: Epigenetics: complexity truly complexity truly increasesincreases

Self-assembly of the virus capsid

Subunits are composed of proteinsSubunits 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, BUTIn a sense yes, BUT A bag of elephant proteins is not an A bag of elephant proteins is not an

elephantelephant Structure that self-assembleStructure that self-assemble

Virus particlesVirus particles The formation of spongesThe formation of sponges

Limitations of the jigsaw puzzle principleLimitations of the jigsaw puzzle principle

Wave-like properties of development

Wave forms are largely independent of Wave forms are largely independent of chemical compositionchemical composition

Animal coat patterns (zebra, tiger, etc.)Animal coat patterns (zebra, tiger, etc.) BUT altered genes can alter the shape of the BUT altered genes can alter the shape of the

elephantelephant Somehow molecules determine form even if Somehow molecules determine form even if

they do not self-assemblethey do not self-assemble BUT HOW?BUT HOW?

The lesser know work of Alan Turing

English mathematicianEnglish mathematician Breaking of the german Breaking of the german

codecode Creator of the „universal Creator of the „universal

Turing machine”Turing machine” His relevant paper: His relevant paper:

Philosophical Philosophical Transactions of the Royal Transactions of the Royal Society Society (1952)(1952)

What is behind animal What is behind animal coat patterns?coat patterns?

Theory of a chemical standing wave

Two compounds: an Two compounds: an activator and an inhibitoractivator and an inhibitor

The activator helps its The activator helps its own formationown formation

Inhibitor inhibits the Inhibitor inhibits the formation of the activatorformation of the activator

Both compounds degradeBoth compounds degrade Inhibitor diffuses much Inhibitor diffuses much

fasterfaster

A kémiai állóhullám

In a well-stirred medium both concentrations reach In a well-stirred medium both concentrations reach equilibriumequilibrium

If the solution is not stirred, then a positive fluctuation in If the solution is not stirred, then a positive fluctuation in activator concentration will enhance itselfactivator concentration will enhance itself

Fluctuation is due to chanceFluctuation is due to chance Inhibitor concentration also rises, but its higher diffusion Inhibitor concentration also rises, but its higher diffusion

rate decrease the amplituderate decrease the amplitude

The coat of a fish

Growth as well as REGENARATION seems to Growth as well as REGENARATION seems to follow a Turing mechanismfollow a Turing mechanism

Reaction-diffusion systemsReaction-diffusion systems

Wolpert: a „French flag”

A simple model of pattern formation

Positional information and pattern formation

Each person has a Each person has a specific seat in the specific seat in the stadiumstadium

In each seat a specific In each seat a specific poster must be shownposter must be shown

Hair patterns in Oncopeltus as indicator of polarity

Hairs point backwards on the cuticuleHairs point backwards on the cuticule Removal of segment boundary reverses the Removal of segment boundary reverses the

direction of hair growthdirection of hair growth

Development of the chick limb

The zone of polarizing activity (ZPA) directs the The zone of polarizing activity (ZPA) directs the formation of the order of digitsformation of the order of digits

The effect of ZPA

Prepattern and consequence

Morphogen is the Morphogen is the sonic hedgehogsonic hedgehog protein protein

Again the axis of Drosophila

The expression of maternal bicoid mRNA

Both mRNA and Both mRNA and protein can be protein can be visualized by visualized by appropriate appropriate compoundscompounds

Determination of the 2nd even-skipped (eve) stripe

Bicoid and hunchback Bicoid and hunchback proteins activateproteins activate

Giant and Krüppel Giant and Krüppel inhibitinhibit

Not too elegant!Not too elegant!

Gene expression and pattern

Combinatorial Combinatorial determinationdetermination

Vizsgaidőpontok

Január 7, 14, 21, 28 KEDDEK, Szabó Január 7, 14, 21, 28 KEDDEK, Szabó József terem 10-12 óraJózsef terem 10-12 óra

Január 9, 16, 23 CSÜTÖRTÖKÖK, Szabó Január 9, 16, 23 CSÜTÖRTÖKÖK, Szabó József teremJózsef terem