Lecture 16- Polarity

● Understand the importance of cell polarity in facilitating morphology and function of different cell types. ● Understand how genetic studies, especially in C. elegans have been key to our current understanding of cell polarity. ● Understand the idea that establishment of polarity involves distinct but conserved groups of proteins that define parts of the membrane and lead to changes in cytoskeleton organisation and membrane trafficking.

What important ability of migrating fibroblasts is a result of polarity?

The front of the cell dragging the back

What are migrating fibroblasts relevant to?

development and understanding disease metastasis

How do vesicles help generate cellular polarity?

By transporting specific proteins, lipids and signalling molecules (forwards and backwards) along a microtubule network

What two types of polarity do epithelial cells arranged in sheets have?

Apical basolateral and Planar Cell Polarity

How is actin organised in the cytoskeleton?

in a cortex just underneath the cell surface

What is actin attached to and what does this allow?

cytoskeleton spectrum, movement

What does immunofluorescence allow us to visualise?

tight junction protein’s role

What is the role of adherin?

helps bind cells and facilitate intercellular communication

How does the organisation of proteins help create cellular polarity?

regions of the cell have distinct protein compositions, allowing different capabilities, morphologies and functions

Give examples polarity within neuronal cells

dendrites vs cell body

Which one of these is not a reason polarity is important in animals

environmental responses

Give an example of how plants display polarised growth

plants growing upwards

Briefly describe the discoveries of Whitman’s 1878 leech experiment

cell has different components and some go to one daughter and some go to another, differences in daughter cells were reflected in the different lineages

Briefly describe the discoveries of Conklin’s 1905 experiment with ascidian (sea squirt) oocytes

identified 5 different cytoplasm types in the oocyte that were differentially inherited to determine different tissue types

Why were Whitman and Conklin’s experiments key?

They laid the foundations of modern developmental genetics and biology

What are the two main routes of generating diversity?

Intrinsic and extrinsic division

Briefly outline intrinsic division

polar mother cells divide and daughters inherit different components

Briefly outline extrinsic division

daughters equal at birth but are exposed to different environmental signals

What are the two types of extrinsic signalling

from other cells, between sister cells

What are the two types of intrinsically generated polarity

localised determinants, asymmetric division plane

What role does the mother cell’s polarity play in generating diversity in intrinsic cell fate decisions

The mother cells polarity results in the daughters inheriting different components

What qualities of C.elegans make them good model organisms for studying cell fate?

transparent and easy to visualise, fixed number of somatic cells, fates have been mapped

How many founder cells does c.elegans have?

six

How does c.elegans divide?

asymmetrically

What is the difference between apical basolateral polarity and planar polarity?

Apical basolateral polarity has distinct top (apical) and bottom (basolateral) sides in epithelial cells, while planar polarity refers to the orientation of cells relative to each other in a tissue.

What did the c.elegans genetic screen to study asymmetric cell division reveal?

Par (partitioning defective) genes

Briefly describe what was seen in Par mutants?

size and fate difference between daughter cels were less pronounced

What was seen in EXTREME Par mutants?

two daughter cells identical

What were the two daughter cells involved in Par protein discovery in C.elegans?

AB and P1

What proteins do the par genes encode?

Par proteins 1-6 and aPKC (atypical protein kinase)

Are all the par genes/ proteins conserved in other metazoans?

No, Par2 is not conserved

What event breaks symmetry in a developing organism

fertilisation

What determines the axis of polarity?

the sperm entry point

Which pole does the sperm entry point become?

posterior

What does the sperm deliver?

microtubule organising centre

Briefly outline what the microtubule organising centre does

anchors microtubules, par proteins involved in antagonism allowing some proteins to accumulate at the anterior pole and preventing posterior pole migration

List the early stages of polarity in cell development

symmetry breaking (sperm entry), polarity established (proteins, antagonism), polarity maintenance (for asymmetric division), mitosis

What key characteristic of polar cells is crucial to maintaining polarity?

distinctly localised feedback loops of phosphorylation

What is the first event in hierarchy of establishing polarity?

microtubules recruiting Par proteins (1 and 2) to posterior complex

What is the second event in hierarchy of establishing polarity?

posterior Par proteins antagonise anterior Par proteins which accumulate at the anterior cortical domain

What is the third event in hierarchy of establishing polarity?

distinct localisation of the Par proteins at the posterior and anterior cortexes and the boundary, requiring a directional force and a cytoskeletal force

where do anterior Par proteins accumulate?

anterior cortical domain

How is polarity maintained?

endocytosis and exocytosis in right place and delivering the right cargos to the right domain

What happens if material is bought to the wrong domain?

re-endocytosed (taken back in) and retargeted to the correct domain

How are invaginations formed during development

size of apical domain smaller/ regulated as the basolateral domain is extended

Give two reasons epithelium maintenance is important

prevent pathogens entering the body, epithelia can give rise to cancer if removed and allowed to circulate

What developmental structure referenced in the lecture is an example of the importance of apical to mesenchymal transition/ invagination?

neural tube formation

What protein is very important for epithelium maintenance in mammals?

Cadherin

What forms the core of a cell polarity network in many animal cells and developmental contexts?

Par proteins

Describe the output of the cell polarity network

one of mutual antagonism with the establishment of opposing and complementary membrane domains that define a cell’s axis of polarity

In which organism was the cell polarity network first discovered and what was the outcome?

in c.elegans, found asymmetric cell divisions in the worm are important for lineage establishment, mutations cause similar daughters

Breifly outline how transcellular glucose transport exemplifies the need for polarity