Chapter 4: JUXTACRINE Mechanisms of Morphogenesis

Question 1

all cells in an embryo are either __ or ___

Answer 1

epithelial: sheets and tubes that adhere to one another

2) mesenchymal: migrate individually or in a group. Forms a variety of tissues.

Question 2

Homophilic binding

Answer 2

binding between 2 SAME receptors on dif cells

Question 3

heterophilic binding

Answer 3

binding between 2 dif receptor types (ex/ notch receptor on one cell binding to delta receptor on other cell)

Question 4

alteration of receptor shape after ligand binding/other receptor binds allows for

Answer 4

enzymatic activation that stimulates signalling pathways. Intracellular protein conformational change/enzymatic activation often occurs via cleaving, phosphorylation, cAMP or Ca2+.

Question 5

How are cells able to sort out into their proper embryonic positions through selective affinity?

Answer 5

cells from dif germ layers have dif affinities for each oterh. Ex/ ectoderm has - affinity for endoderm, and + affinity for mesoderm, so its cells will try to be near the mesoderm but far from the endoderm.

Question 6

Differential adhesion hypothesis:

Answer 6

cell sorting patterns are based on thermodynamic principles. Cells form aggregates with the smallest interfacial free energy possible.

Question 7

Interfacial free energy

Answer 7

product of tension and area. The lower the free energy, the more stable.

Question 8

cells with strongeradhesive properties will be ___ to those with weaker adhesion

Answer 8

being strongly adhesive = more central to those with weaker adhesion

Question 9

Enhanced adhesion of cells is caused by

Answer 9

1) increasing the NUMBER of receptors on certain cells

2) presence of specific receptors that bind more tightly.

Question 10

Cadherins are ___ dependent

Answer 10

Ca2+

Question 11

Cadherins are ___ proteins that interact with

Answer 11

trnasmembrane proteins that interact with other cadherins

Question 12

Cadherins are anchored to the cell membrane by __. What does this form?

Answer 12

catenin. These cad-cat protein complexes forms junctions to hold epithelial cells by binding ACITN cytoskeleton of cell to integrate epithelial cells in a mechanical unit.

Question 13

These cad-cat protein complexes forms ____ to hold ____ cells by binding ____ cytoskeleton of cell to integrate epithelial cells in a mechanical unit.

Answer 13

These cad-cat protein complexes forms junctions to hold epithelial cells by binding ACITN cytoskeleton of cell to integrate epithelial cells in a mechanical unit.

Question 14

Blocking cadherin synthesis prevents:

Answer 14

the formation of epithelial tissues and cause the cells to disaggregate.

Question 15

Cadherins found in the embryonic cells

Answer 15

E cadherins

Question 16

cadherins in the placenta

Answer 16

P cadherin

Question 17

Cadherins in the nervous system

Answer 17

N cadherin

Question 18

R cadherin

Answer 18

cadherin in the retina.

Question 19

Procadherin

Answer 19

cadherins that don’t bind to catenin. Keeps migrating sheets of cells together.

Question 20

Catenin is on the ___ side in a cadherin junction

Answer 20

catenin is on the intracellular side. Allows cadherin to bind to actin. Calcium binds to the extracellular side of cadherin.

the extracellular domain adheres the cells together, and th e internal domain links to catenin which attaches to actin and provides mechanical forces, allowing for formation of sheets and tubes.

Question 21

the ___ cadherin, the stronger the tension and attachment between cells

Answer 21

the more cadherin, the stronger the attachment between cells. the ability of cells to sort themselves based on the amount of cadherin expression.

Question 22

If you stuck cells containing either P or E cadherin in a jar together, how would they aggregate?

Answer 22

P cadherin has higher binding affinity for each other than E cadherin. cells with P cadherins would aggregate inside the E cadherin cells.

Question 23

extracellular matrix

Answer 23

the environment surrounding cells

Question 24

List components of ECM

Answer 24

• collagen
• proteoglycans
• glycoproteins (fibronectin and laminin)

Proteoglycans have long chains with disaccharide as repeating structures. Glycoproteins have short highly branched glycan chains with no repeating unit

Question 25

proteoglycans of the ECM are extracellular proteins in the ECM that contains ____ polysaccharides. What does it allow the ECM to do?

Answer 25

contains glycosaminoglycan polysaccharides. Involved in allowing the ECM to act as a paracrine factor

Question 26

Outline two prominent proteoglycans found in the ECM

Answer 26

1) Heparen Sulfate: binds to different families of paracrine factors and assists in presenting these factors to their receptors. Ex/ In order for HH to be secreted as a lipoprotein, it first binds to heparan sulfate before acting on the responding cell. Also involved in bacterial determinatino about gram +/-
2) Chondroitan Sulfate: provides structural integrity to cartilaginous structures.

Question 27

Fibronectin is a ____ dimer that forms fibronectin ____. What are three functions?

Answer 27

Glycoprotein dimer that forms fibronectin Fibrils

• allows proper alignment of cells in the ECM by containing specific binding sites
• links cells together via fibronectin-integrin interactions and to collegen and other proteoglycans
• role in cell migration: serves as a PATH for migrating cells. Ex/ Fibronectin moves germ cells into the gonads.

Question 28

___ assembles ECM, promoting cell adhesion and growth, changing the shape of cells and cell migration. It’s similar to Fibronectin

Answer 28

Laminin, a glycoprotein

Question 29

____ and ______ ____ Are major components of the basal lamina

Answer 29

Laminin and Type 4 Collagen are major components of the basal lamina: made of closely knit sheets that lay under epithelial cells.

Question 30

Primary receptor for fibronectin

Answer 30

Integrins.

Question 31

What AA sequence is required for fibronectin to bind to integrins?

Answer 31

Integrins bind to the RGD (arginine-glycine-aspartic acid) sequence of fibronectin extracellularly

Question 32

on the extracellular side, integrins bind to ____, on the intrecellular side of an integrin, it binds to ___ and ____ which are connected to ___ ____

Answer 32

on the extracellular side, integrins bind to FIBRONECTIN, on the intrecellular side of an integrin, it binds to TALIN and ALPHA ACTININ which are connected to ACTIN FILAMENTS.

• ALLOWS THE CELL TO MOVE BY CONTRACTING ACTIN FILAMENTS AGAINST THE FIXED EXTRACELLULAR MATRIX.

Question 33

HOW MANY SUBUNITS IN AN INTEGRIN

Answer 33

2- alpha and beta. Alpha contains calcium binding sites, and beta subunit binds fibronectin, talin and alpha actinin.

Question 34

3 Functions of integrins

Answer 34

1) allows the cell to move by contracting the actin-alphaactinin- talin component that is bound to the intracellular side of integrin
2) triggers gene expression
3) important for apoptosis prevention

Question 35

detachment of ECM fibronectin to a cell’s integrin results IN:

Answer 35

anoikis: death on detatchment apoptoses. Occurs when the adhesions connecting cells to ECM becomes broken, resultin in caspase pathway activation. Possible cancer treatment.

Question 36

Explain the mouse mammary gland experiment and how ECM is important for cell growth and differentiation

Answer 36

1) Cells plated with NO ECM: cell division occured (cmyc and cyclin D1 expressed)
- no cell differentiation (catenin, lactoferrin, WAP OFF)

2) if cells played on basal lamina: cells STOP DIVIDING (cmyc and cyclin D1 OFF), cell differeniation STARTS (first catenin, then WAP, lactoferrin ON).
- cell differentiation occurs when intrgrins from the cell membrane bind to the laminin of the basal laminin

3) mammary gland cells envelope themselves in the basal lamina, forming secretory epithelium.
- binding of integrins is necessary for cell division; it activates the CASEIN gene and acts in concert with PROLACTIN

Question 37

when was differentiation seen in the mouse mammary gland after being plated on basal lamina?

Answer 37

cell differentiation occurs when intrgrins from the cell membrane bind to the laminin of the basal laminin

• cmyc and cyclin D1 turned OFF –> no cell growth
• catenin, lactoferrin and then WAP AND P21 turned ON –> Differentiation.

Question 38

binding of integrins is necessary for cell division; it activates the CASEIN gene and acts in concert with PROLACTIN

Answer 38

binding of integrins is necessary for cell division; it activates the CASEIN gene and acts in concert with PROLACTIN
- in addition to casein, lactoferrin and WAP is also turned on.

Question 39

events where epithelial cells are transformed into mesenchymal cells

Answer 39

Epithelial-mesenchymal transition.

Question 40

epithelial is originally stationary and interacts with ___ ___. During EMT, it becomes a migratory ___ cell that can invade tissues and help form new organs.

Answer 40

epithelial is originally stationary and interacts with BASAL LAMINA. During EMT, it becomes a migratory MESENCHYMAL cell that can invade tissues and help form new organs.

Question 41

EMT occurs via ____ ___ that instruct target cells to do 4 things:

Answer 41

EMT occurs via paracrine factors that instruct target cells to:

1) down regulate cadherins – less attachment between cells
2) down regulate integrin connections to laminin in the basal laminin
3) rearrange actin cytoskeleton
4) secrete new extracellular matrix molecules that are characteristic of mesenchymal cells.

• enzymes break down the basal lamina, and the detached epithelial cells can squeeze out to form the mesenchyme underneath. the basal lamina then shifts to bring the cells back together.

Question 42

What is Epithelial mesenchymal transition used for

Answer 42

1) formation of neural crest cells from the dorsal region of the neural tube
2) formation of mesoderm in chick embryo
3) formation of vertebrate precursor cells
4) wound healing
5) cancer metasis: cells from a solid tumor break off to invade other tissues. Requires down regulation of cadherin, basal lamina breakdown, actin rearrangement.

Question 43

when a group of cells communicate with an adjacent cell set to change the behaviour of developmental end point of target cells

Answer 43

induction

Question 44

in order for a cell to be a responder to an inducer, it MUST

Answer 44

1) contain a receptor for the molecule/receptor/cell that it is trying to interact with
2) must have the ability to respond to the signal when it’s receptor gets stimulated

Question 45

competance

Answer 45

the ability of a cell to receive and respond to and inductive signal.

Question 46

reciprocal induction

Answer 46

inducer becomes the responder, and responder becomes the inducer.

Question 47

two types of induction interactions

Answer 47

1) instructive interactions: signal from the inducer is necessary for initiation of GENE EXPRESSION expression in the responder

2) permissive interaction: responder IS ALREADY SPECIFIED – only requires an environment that allows expression of its specialized traits/functions.
- the environment/ECM does not alter the type of cell that is produced, but it enables what has already been determined to be expressed.