jenkins2 - establishment of cell polarity

7/24/2019 JENKINS2 - Establishment of Cell Polarity

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Lecture 2

Establishment of

Cell Polarity

Prof. Gareth I. Jenkins

[email protected]



The acquisition of assymetry - ‘polarity’ - is a

key step in early development as it leads to the

production of cells with different properties and

hence different developmental fates

A simple example…..



The Fucus zygote is an excellent system to study

the acquisition of polarity

The zygote is

initially apolar

Polarity determines cell fate



Fucus zygote polarity is influenced by

environmental factors

light Rhizoid develops on shaded side

Takes 12 h to appear

Polarity not fixed until > 10 h

- fertilization (rhizoid at entry point)

- heat (rhizoid to warm side)

- pH and salt (rhizoid to alkaline pH andsalt)

- Electrical gradient (rhizoid at -ve pole)

In addition polarity is

determined by:



Polarizing zygotes generate an electrical voltage

Rhizoid end

light

+ve

-ve

Implies that development of

polarity is accompanied by

production of ionic gradients



Ca2+ efflux

Ca2+ influx

Rhizoid end

Calcium is involved in establishing polarity

Localisation of Ca2+ channels is

observed after 5-6 h of illumination

Disruption of calcium

gradient prevents

development of polarity



However in many plant and animal systemsthe zygote is not initially apolar but already

has an assymetric distribution of

components

The assymetry of the zygote reflects a polar

distribution of molecules and organelles in

the egg cell gamete



The polar distribution of components in the

egg cell and hence zygote will give rise to

differences in daughter cell composition anddevelopmental fate following the first

division



What is meant by cell polarity and

why is it important?

Outline how polarity develops in

the Fucus zygote and describe the

factors involved in its control

Question:



The polar distribution of components in the

egg cell and hence zygote will give rise to

differences in daughter cell composition anddevelopmental fate following the first

division

Concept of ‘localised

cytoplasmic determinants’



The polar distribution of components is

sometimes visible, e.g. in amphibian oocytes,

but to show that a component has an effecton development need to demonstrate its

action by e.g. removal or translocation

Animal pole

Vegetal pole

Amphibian oocyte

Albino mutants lackingpigmentation of the oocyte are

not altered in development, so

pigment is not controlling cell

fate



Sea squirt

The polar distribution of

components and their

role in determining cell

fate has been studied in

ascidians

The ascidian egg has regions of

cytoplasm with different

coloured inclusions. These

show reproducible patterns ofdistribution during early

embryogenesis and are linked

to the fate of cells



The regions of the fertilised egg give rise to

different tissues during embryogenesis, i.e.

have localised cytoplasmic determinants

From: Developmental Biology , S.F. Gilbert.

6th Ed. Publ: Sinauer Associates Inc.

http://www.ncbi.nlm.nih.gov/sites/entrez?db=books



Transplantation of cytoplasmic regions into

different parts of the egg give rise to altered

cell fate.

E.g. movement of myoplasm - which gives rise

to muscle cells - into cells which normally give

rise to epidermal cells, results in production of

muscle cells

8-cell embryo

Epidermis

Muscle

myoplasm

Cultured cells

Muscle cells



How does the polar distribution of

components become established?

Address this question by looking at

Drosophila embryo development…..



In Drosophila, anterior-posterior (head to

tail) polarity of the embryo, larva and adult

derives from polarity established in the egg

embryo

anterior posterior



The eggs are produced in

the maternal ovaries. The

precursor to the egg isthe oocyte. Nurse cells in

the ovary synthesise

macromolecules that are

transported to the oocyte as it develops via

cytoplasmic bridges.

Some of these

macromolecules (e.g.particular mRNAs) are

assymetrically

distributed.

From: Developmental Biology , S.F. Gilbert



The Drosophila bicoid mutant has altered

embryo development

The embryo lacks the head and thorax at theanterior end and instead has a second set of

posterior structures

Wild-type

bicoid

anterior posterior

Therefore the wild-

type Bicoid gene

product is requiredfor normal anterior

development of the

embryo From: Developmental Biology , S.F. Gilbert



Bicoid mRNA and

protein are localised

at the anterior end ofthe embryo in wild-

type

mRNA

protein




The bicoid mutant phenotype can be

rescued by injecting wild-type Bicoid mRNA

into the anterior end of the embryo

Shows that the spatial localisation of Bicoid

mRNA is important




How does Bicoid

mRNA become

localised at theanterior pole?

Bicoid mRNA is

synthesised in thenurse cells of the

maternal ovaries and

transferred to the

oocyte where itbecomes localised at

the anterior end




Conclusion: Bicoid encodes a localised

cytoplasmic determinant required for

normal anterior development in Drosophila.Its localisation is established during oocyte

development in the maternal ovary.

Example of a Maternal Effect Gene



Additional Maternal Effect Genes are

involved in determining anterior-posterior

polarity in Drosophila:

• Bicoid and Hunchback regulate production

of anterior structures

•

Nanos and Caudal regulate production ofposterior structures

Bicoid, Hunchback and Caudal are

transcription factor proteins that regulateother genes controlling later steps in

development



Abundance of mRNAs

Abundance of proteins

The Bicoid protein inhibits the

translation of Caudal mRNA at

the anterior pole, resulting in

the accumulation of Caudalprotein towards the posterior

Similarly, Nanos inhibits

translation of Hunchback

mRNA at the posterior

The polar distribution of

Bicoid and Nanos mRNAs

is established in the ovary

The spatial distribution of these proteins

regulates subsequent steps in development




Explain how Bicoid is involved in

Drosophila development

Question:

jenkins2 - establishment of cell polarity

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