Extracellular matrix

Question 1

What is diversity in the ECM due to?

Answer 1

variations in relative amounts of macromolecules and the organisation of those macromolecules
each ECM will be adapted to the functional requirements of the particular tissue

Question 2

What are the functions of the ECM?

Answer 2

functions as adhesive substrate
provides structure
presents growth factors to their receptors
sequesters and stores growth factors
senses and transduces mechanical signals

Question 3

What are the two main macromolecules that compose the ECM

Answer 3

proeotglycans and fibrous proteins (collagens, elastins, fibronectins and laminin)

Question 4

What are the function of proteoglycans

Answer 4

to resist compressive forces and loads, highly hydrated to allow rapid diffusion of nutrients, metabolites and hormones between blood and tissue cells
act as a space filler in development
regulate activities of secreted proteins such as proteases and protease inhibitors

Question 5

What is the structure of proteoglycans

Answer 5

a core protein linked to GAGs

Question 6

What are GAGs and the 4 main groups

Answer 6

GAGs are unbranched polysaccharide chains composed of repeating disaccharide unites. highly negatively charged because of sulphate or carboxylic groups
hyaluronan, chondroitin + dermatan sulphate, heparan sulphate, keratan sulphate

Question 7

What are the differences between the left and right side of the dorsal mesentary which will facilitate gut looping

Answer 7

left side = less hyaluronan, epithelial are cuboidal, increased GAGs and basement membrane components
right side = more hyaluronan acting as a space filler, mesenchymal cells are sparsely distributed so cannot communicate or aggregate

Question 8

What is the function of fibrous proteins in the ECM

Answer 8

strengthen and coordinate organisation of the matrix

Question 9

What is heparan sulphate needed for

Answer 9

FGF signalling and early specification of germ layers. needed for the FGF4 and FGF8 ligands

Question 10

What is syndecan-1

Answer 10

a family of 4 transmembrane proteoglycans which bind HS chains and other proteins
allows communication between extracellular and inside the cell

Question 11

What is the function of syndecan-2

Answer 11

sequesters growth factors through GAG sidechains (HS/CS)
may increase the affinity for GF binding to their receptors
also specifies L/R asymmetry in heart/gut looping

Question 12

What does the stiffness of the ECM lead to

Answer 12

driving different cell differentiation

Question 13

Which cells will differentiate from the following ECM:
- soft matrices
- stiffer
- rigid

Answer 13

soft matrices = neurogenic
stiffer = myogenic
rigid = osteogenic

Question 15

What is the repeating amino acid sequence in collagen?

Answer 15

Gly-X-Y

Question 16

What are the most common collagen types?

Answer 16

Most common collagens types:
Type I: skin, tendon, vascular ligature, organs, bone
Type II: Cartilage
Type III: reticulate (commonly found in type 1)
Type IV: Basal lamina (epithelium-secreted layer of basement membrane)
Type 5: cell surfaces, hair and placenta

Question 17

What is the function of collagen?

Answer 17

Resist tensile forces in skin for example ae woven in a wickerwork pattern to resist tensile stress in multiple directions

Question 18

What is Elastin needed for?

Answer 18

Skin, blood vessels lungs that require strength and elasticity

Question 19

What is Fibronectin?

Answer 19

Guides cell migration in vertebrate embryos
Need to make mesoderm

Essential for cleft formation during initiation of epithelial branching and is accompanied by an adjacent loss of E-cadherins

Question 20

What happen when Fibronectin is knocked out?

Answer 20

Shortened anterior posterior axis
Abscence of somites
Deficit in mesenchyme

Question 21

What are integrins?

Answer 21

Large family of heterodimeric glycoprotein receptors
Exist as two non covalently bound alpha and beta subunits
Bind variety’s of ECM molecules e.g collagen, Fibronectin, laminins

Question 22

What is the function of integrins?

Answer 22

• Attaching cell to ECM
  Cell migration in
  Transduction signals from ECM to cell

Question 23

What happens if a mutation occurs in a5 B1 chain?

Answer 23

Cannot bind to Fibronectin- which acts as a cell communicator

Question 24

What are the types of way cells can communicate between each other?

Answer 24

Tight junction
Cell-cell anchoring junctions
Channel forming junction
Cell-matrix anchoring junctions
- Actin-linked cell matrix junctions
Hemidesmosome
Gap junction
Desmosomes
Adherens junction
Tight junction

Question 25

What molecule communicate between cells and ECM?

Answer 25

Integrins and sydecans

Question 26

What are cadherins?

Answer 26

A cell adhesion molecule involved in formation of Adherens junctions Ca2+ dependent: extracellular domain facilitates cell-cell crosstalk and project out of cells and intracellular domain binds number of signalling and adaptor proteins Behave as a recpetor and ligand O from a junction

Question 27

What are cadherins involved in during development?

Answer 27

• Positing of cells • Responsible for separation of different tissue layers • Cell migration

Question 28

What is the role E-cadherins?

Answer 28

Epithelium

Question 29

What is N-cadherins involved in ?

Answer 29

Neuralation- expression alters as neural plate forms

Question 30

What are Desmosomes?

Answer 30

They link Intracellular to the intermediate filaments cytoskeleton form adhesiveness bonds in a network that gives mechanical strength In epidermis and myocardium and subject to mechanical force Stick together- hard to pull apart

Question 31

What are gap junctions?

Answer 31

Channels composed of connexins, which connect cytoplasm to two adjacent cells of small molecule - Ion/water transport

Question 32

What is a stem cell niche?

Answer 32

Stem cells reside in dynamic specialised micro environment - a niche

Question 33

Why is it important or proper bonding between stem cells and their niche essential?

Answer 33

To maintain stem cell pool for long term self renewal

Question 34

How are developmental processes regulated?

Answer 34

Cell-cell interaction Systemic or exogenous factors Endogenous factors Matrix interaction Shape and polarity

Question 35

Why is the ECM vital to the stem cell niche?

Answer 35

Why is THE ECM vital to the stem cell niche? 1. Anchorage restricts stem cell in niche- exposure to Paracrine and cell-cell contact signals 2. Anchorage- vital for orienting mitotic spindle to enable stem cells to undergo asymmetric cell division: essential for self renewal and generation of daughter cells destined to undergo differentiation 3. Maintains stem cell properties e.g biomechanics (ECM stiffness) affects cell fate determination

Question 36

If a stem cell is sitting in a stiff ECM what is it likely to become?

Answer 36

Cartilage for bones

Question 37

How do Haematopoietic stem cells DEVELOP

Answer 37

They develop during embryogenesis in complex process involving multiple anatomical sites Once HSC precursors have been specificed from mesoderm they mature into function HSCs and undergo self needing division to generate a pool of HSCs which colonise the bone marrow at birth

Question 38

What are osteopontins?

Answer 38

One of the main glycoproteins secreted by osteoblasts essential for HSC numbe and function

Question 39

What happens when osteopontin is knocked out?

Answer 39

Enhance cyclising of HSCs, negatively regulates stem cell pool- acts as a brake

Question 40

How do HScs adhere to osteopontin?

Answer 40

Bind to a1B1 and a5B1 integrins - restricting expression to endosteal region

Question 41

Where are intestinal stem cell niches found? How are they formed?

Answer 41

Found in glandular crypts of small and large intestine. Formed by epithelial invaginations into the ECM by supportive stroma cells

Question 42

What ECM molecules are in intestinal stem cell niches?

Answer 42

GAGs, Type VI collagen Fibronectin, integrins, laminin a5