Chapter 4: JUXTACRINE Mechanisms of Morphogenesis Flashcards
all cells in an embryo are either __ or ___
epithelial: sheets and tubes that adhere to one another
2) mesenchymal: migrate individually or in a group. Forms a variety of tissues.
Homophilic binding
binding between 2 SAME receptors on dif cells
heterophilic binding
binding between 2 dif receptor types (ex/ notch receptor on one cell binding to delta receptor on other cell)
alteration of receptor shape after ligand binding/other receptor binds allows for
enzymatic activation that stimulates signalling pathways. Intracellular protein conformational change/enzymatic activation often occurs via cleaving, phosphorylation, cAMP or Ca2+.
How are cells able to sort out into their proper embryonic positions through selective affinity?
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.
Differential adhesion hypothesis:
cell sorting patterns are based on thermodynamic principles. Cells form aggregates with the smallest interfacial free energy possible.
Interfacial free energy
product of tension and area. The lower the free energy, the more stable.
cells with strongeradhesive properties will be ___ to those with weaker adhesion
being strongly adhesive = more central to those with weaker adhesion
Enhanced adhesion of cells is caused by
1) increasing the NUMBER of receptors on certain cells
2) presence of specific receptors that bind more tightly.
Cadherins are ___ dependent
Ca2+
Cadherins are ___ proteins that interact with
trnasmembrane proteins that interact with other cadherins
Cadherins are anchored to the cell membrane by __. What does this form?
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.
These cad-cat protein complexes forms ____ to hold ____ cells by binding ____ cytoskeleton of cell to integrate epithelial cells in a mechanical unit.
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.
Blocking cadherin synthesis prevents:
the formation of epithelial tissues and cause the cells to disaggregate.
Cadherins found in the embryonic cells
E cadherins
cadherins in the placenta
P cadherin
Cadherins in the nervous system
N cadherin
R cadherin
cadherin in the retina.
Procadherin
cadherins that don’t bind to catenin. Keeps migrating sheets of cells together.
Catenin is on the ___ side in a cadherin junction
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.
the ___ cadherin, the stronger the tension and attachment between cells
the more cadherin, the stronger the attachment between cells. the ability of cells to sort themselves based on the amount of cadherin expression.
If you stuck cells containing either P or E cadherin in a jar together, how would they aggregate?
P cadherin has higher binding affinity for each other than E cadherin. cells with P cadherins would aggregate inside the E cadherin cells.
extracellular matrix
the environment surrounding cells
List components of ECM
- 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
proteoglycans of the ECM are extracellular proteins in the ECM that contains ____ polysaccharides. What does it allow the ECM to do?
contains glycosaminoglycan polysaccharides. Involved in allowing the ECM to act as a paracrine factor
Outline two prominent proteoglycans found in the ECM
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.
Fibronectin is a ____ dimer that forms fibronectin ____. What are three functions?
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.
___ assembles ECM, promoting cell adhesion and growth, changing the shape of cells and cell migration. It’s similar to Fibronectin
Laminin, a glycoprotein
____ and ______ ____ Are major components of the basal lamina
Laminin and Type 4 Collagen are major components of the basal lamina: made of closely knit sheets that lay under epithelial cells.
Primary receptor for fibronectin
Integrins.
What AA sequence is required for fibronectin to bind to integrins?
Integrins bind to the RGD (arginine-glycine-aspartic acid) sequence of fibronectin extracellularly
on the extracellular side, integrins bind to ____, on the intrecellular side of an integrin, it binds to ___ and ____ which are connected to ___ ____
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.
HOW MANY SUBUNITS IN AN INTEGRIN
2- alpha and beta. Alpha contains calcium binding sites, and beta subunit binds fibronectin, talin and alpha actinin.
3 Functions of integrins
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
detachment of ECM fibronectin to a cell’s integrin results IN:
anoikis: death on detatchment apoptoses. Occurs when the adhesions connecting cells to ECM becomes broken, resultin in caspase pathway activation. Possible cancer treatment.
Explain the mouse mammary gland experiment and how ECM is important for cell growth and differentiation
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
when was differentiation seen in the mouse mammary gland after being plated on basal lamina?
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.
binding of integrins is necessary for cell division; it activates the CASEIN gene and acts in concert with PROLACTIN
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.
events where epithelial cells are transformed into mesenchymal cells
Epithelial-mesenchymal transition.
epithelial is originally stationary and interacts with ___ ___. During EMT, it becomes a migratory ___ cell that can invade tissues and help form new organs.
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.
EMT occurs via ____ ___ that instruct target cells to do 4 things:
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.
What is Epithelial mesenchymal transition used for
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.
when a group of cells communicate with an adjacent cell set to change the behaviour of developmental end point of target cells
induction
in order for a cell to be a responder to an inducer, it MUST
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
competance
the ability of a cell to receive and respond to and inductive signal.
reciprocal induction
inducer becomes the responder, and responder becomes the inducer.
two types of induction interactions
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.
