Drosophila dorsal/ventral axis detemination

How are different tissue types specified at distinct positions on the embryonic dorsal-

ventral axis?

amnio-serosa dorsal

ectoderm

neuro-ectoderm

mesoderm

Cell fate specification at the blastoderm stage

mesoderm formationfate map

dorsal

ventral

Dorsal-Ventral fate map

Genes identified in a famous screen for Drosophila mutants with embryo patterning defects

Torpedo

Gurken

Localized maternal mRNA sets up anterior and posterior poles

Gurken protein specifies the Anterior-Posterior axis of the Drosophila embryo during oogenesis

(Similar to EGF)

Gurken also signals dorsal pole formation during oogenesis

follicle cells

anterior posterior

A P

V

DD

V

-+-

microtubules

71-6 810A

gurken expression in the oocyte

10A

gurken expression in the

oocyte

1-6

migration of nucleus

+

-

-

8

oocyte nucleus

Expression of the Gurken Message and Protein Between the Oocyte Nucleus and the Dorsal Anterior Cell Membrane

Gurken signaling inhibits production of an extracellular signal (Spätzle) by follicle cells

follicle cells

Oocyte

pipe expression

Ventral follicle cell

Pipe (Golgi?)

XX

Nucleus

Wind (ER?)

XX

XX

modified from van Eeden & St.Johnston

Gurken = Epidermal Growth Factor (EGF)

Torpedo = EGF receptor(in follicle cells)

Toll Tl - membrane receptor

cactus cact - cytoplasmic inhibitor

of Dorsal nuclear

translocation

dorsal dl - transcription factor

(morphogen)

tube - cytoplasmic protein

pelle - ser/thr protein kinase

Somatic (follicle cells)

ndl, pipe, wbl

gd, snk, ea - serine proteases

Spätzle spz - ligand

Germline (nurse cells)

Dorsal protein

dorsal RNA

Toll protein

Spätzle proteinDorsal protein

nudel, pipe, wbl

amnio serosa

dorsal ectoderm

neuro-ectoderm

mesoderm

Dl nuclear protein

Maternal effect mutations in dorso-ventral patterning

Wild type

ventralized

dorsal

mutant

cactus

mutant

dorsalized T1

T2

T3

A1

A2

A3

A4

A5 A6 A7 A8

dorsal and cactus mutants (maternal germline effect)

dorsal

ventral

Wild type toll mutant cactus mutant

Translocation of Dorsal protein into ventral nuclei but not lateral or dorsal nuclei

Generation of Dorsal-Ventral Polarity in Drosophila

Generation of Dorsal-Ventral Polarity in Drosophila

Wild type

toll mutant

Inject wild-type cytoplasm

mesoderm

neuro-ectoderm(denticle belts)

dorsal ectoderm

The Toll pathway in dorso-ventral pattern formation

into toll mutant eggs

dorsalized

local

rescue

ventral

dorsal

polarity reversal

Conserved pathway for regulating nuclear transport of transcription factors in Drosophila and mammals

Cells with highest nuclear Dorsal levels become mesoderm

Zygotically expressed genes

Action of Dorsal protein in ventral cells

Action of Dorsal protein in ventral cells

High affinity for promoter,Not much Dorsal needed to activate

Action of Dorsal protein in ventral cells

Lower affinity for promoter,More Dorsal needed to activate

Zygotically expressed genes

Action of Dorsal protein in ventral cellsSnail repression of rhomboid creates domains with distinct gene expression patterns

twist

dpp

Dorsal protein

dorsal RNA

Toll protein

Spätzle protein

Dorsal protein

nudel, pipe, windbeutel

Dorso-ventral pattern formation: summary

oocyte nucleus dorsal> repression of ventral fate

in dorsal follicle cells

ventral production of ligand> activation of Toll receptor

> graded nuclear uptakeof Dorsal morphogen

> regulation of zygotictarget gene expression

> cell fates along DV axis

Use of a similar regulatory system to pattern insects and vertebrates

Patterns mesoderm in vertebrates

Patterns ectoderm in Drosophila

Gastrulation in Drosophila

Schematic representation of gastrulation in

Drosophila

Anterior-posterior patterning in Drosophila

The fly body plan: each segment has a unique identity and produces distinctive structures

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

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