Anterior-posterior patterning in Drosophila

The fly body plan: Each segment has a unique identity and produces distinctstructures

3 head

3 thorax

8 abdomen

fate map larva

wild-type

anterior bicoid

posterior oskar

terminal torso

Mutations affecting the antero-posterior axis 3 independent maternal systems: anterior, posterior, terminal

single mutants double mutants

triple mutants

additive phenotypes

active systems

A P T

- P T

A - T

A P -

- - -

- P -

- - T

A - -

active systems

Maternal effect mutations

Zygotic effect mutations

Embryo from wild-type mother

Embryo from bicoid mother

bicoid mutant phenotype

Wild-type Bicoid promotes anterior fates and inhibits posterior fates.

Wild type

blastoderm fate map

bicoid mutant

Anterior: bicoid is required for head and thorax

abdomen abdomenhead

+ thorax

Bicoid mRNA localization in embryo(tethered to microtubules)

Nuclei divide without cell division in Drosophila to produce a syncytial blastoderm

embryo

Fig. 9.1

Bicoid protein gradient in syncytial blastoderm embryo- diffuses after translation from localized mRNA- protein unstable

Transplantation of egg cytoplasm An organizer of the anterior-posterior pattern is located at the anterior pole

wt

rescue of

pattern

wt

head in the center

polarity reversal

wt

thorax at posterior pole

polarity reversal abdomen only

polarity normal

bicoid mRNA

bicoid mRNA induces head and thorax

bicoid (bcd) gene encodes a homeo-domain transcription factor

Injection of bicoid mRNA:anterior (head) structures at site of injection

no head

& reorganization of polarity

Bicoid protein: transcriptional and translational regulator

zygotic target genes maternal target mRNA

(promotes anterior fates) (inhibits posterior fates)

Transplantation of egg cytoplasm Posterior cytoplasm also has polarizing activity

wt

rescue of

pattern

wt

head in the center

polarity reversal

wt

thorax at posterior pole

polarity reversal

wt

double abdomen

polarity reversal abdomen only

polarity normal

fate map larva

wild-type

anterior bicoid

posterior oskar

terminal torso

Mutations affecting the antero-posterior axis 3 independent maternal systems: anterior, posterior, terminal

single mutants double mutants

triple mutants

additive phenotypes

active systems

A P T

- P T

A - T

A P -

- - -

- P -

- - T

A - -

active systems

Nanos is the maternal effector of the posterior system

rescue of all posterior-system mutants

by injection of nanos mRNA

mutant rescued rescued

Embryonic polarity genes

Anterior-Posterior pattern formation in flies

The Bcd gradient is converted into domains of gene expression

Bcd protein binds differentially to enhancers of target genesDifferent thresholds of Bcd concentration are required to turn on different genes

target genes are zygotically expressed Gap genes

low affinity

high affinity

bcd mRNA

Bcd protein

target genes

Bcd gradient and expression domains of target genes

Expression patterns of proteins encoded by Gap genes

Bicoid and Nanos regulate Gap gene expression

Gap gene mutants lack different body regions

Wild type Krüppel hunchback knirps

Gap gene mutants lack different body regions

Hunchback Krüppel

The gap genes regulate each other and form domains with distinct combinations of gene expression.

Anterior-Posterior pattern formation in flies

Wild type

fushi tarazu mutant

Pair-rule mutants

Even-skipped expression pattern

08_18_reporter.gene.jpg

Modularity of the Drosophila even-skipped promoter

parasegment

Krüppelhunchback giant eve stripe #2

repressorrepressor

activator

1 2 3 4 5

Regulation of expression stripe no. 2 of Even-skipped (eve)

multiple binding sites in enhancer of eve repressorsactivators

Regulation of the Second Stripe of Transcription from the even-skipped Gene

Regulation of the even-skipped gene

Fushi tarazu expression

early

late

Eve, Ftz expression

Refinement of expression domains over time

Refined expression domains in distinct cell rows

Anterior-Posterior pattern formation in flies

Segment polarity mutants

Segment polarity mutants

Wingless signaling specifies cell fates in the ventral epidermis

arm mutantWild type

AnteriorcellsmakeHair

PosteriorcellsmakeNakedcuticle

Expression of segment polarity gene wingless

02 4 6

8

1012

LA

fghg

ap

1 3 57

9

1113

Segment polarity genes – 14 stripes

Segments and Parasegments

The Even-skipped and Fushi tarazu pair-rule transcription factors activate the segment-polarity gene Engrailed

Intercellular feedback maintains pair-rule gene expression states

Intercellular feedback maintains pair-rule gene expression states

=Wnt

Wnt signaling pathway

-

+ -

-

-

-

-

+

+

+

+

+

Gradients of Wingless and Hedgehog pattern each segment

Anterior-Posterior pattern formation in flies