Cellular & Molecular Mechanisms of Development I: Interaction and Apoptosis Flashcards
Cells have differential affinities. What does this mean?
certain types of cells show a clear affinity for each other, while apparently avoiding or ignoring contacts with adjacent tissues
Ex:
- mesodermal cells form a continuous sheet, while at the same time smoothly moving between the ectodermal and endodermal germ layers.
- also during formation of neural tissues, the cells of the neural plate show specific interactions that are not shared with the underlying mesoderm or the adjacent, non-neural ectoderm.
Different cells show affinity for each other due to the presence of what?
specific cell adhesion molecules on their surface
*these molecules fall into 3 general classes
What are the three general classes of adhesion molecules?
- calcium independent cell adhesion molecules (CAMs; Ig molecules; ex: neural cell, N-CAM, platelet endothelial cell, PE-CAM)
- calcium depenndent adhesion molcules (cadherins; neural, N-cadherin, epithelial, E-cadherin)
- sugar-mediated adhesion (protein on surface of one cell binds to polysaccharide (sugar polymer) on surface of another cell; ex: selectins, L-selectin)
Calcium independent cell adhesion molecules
- these are members of the immnoglobulin superfamily of proteins
- include neural cell adhesion molecule (N-CAM) and platelet endothelial cell adhesion molecule (PE-CAM)
etc
Ig domains are what kind of binding domains?
- protein-protein binding domains
- they stick light chains and heavy chains together
- two CAMs interact via their Ig domains, the two cells adhere due to many CAM interactions
- antibody molecule: different protein chains interact via the Ig domains
(proteins on two different cells that express these Ig molecules will stick together)
Calcium dependent adhesion molecules called cadherins
- the calcium forms a bridge between two cadherins on different cells
calcium binding domains, calciums form bridges between different cells
cadherin proteins interact with each other via a Ca++ bridge
ex: neural cadherin (N-cadherin) and epithelial cadherin (E-cadherin)
Sugar-mediated adhesion molecules
- proteins on one cell bind to polysaccharides (sugar polymers) on another cell
ex: L-selectin (cynsitiotrophoblast, blastocysts, bound to wall of uterus which has glycoproteins on surface; it is required for implantation of the embryo into the uterine wall, like tennis ball on Velcro)
Cell adhesion molecules may also be linked to what?
signaling pathways
*ex: N-CAM cytoplasmic domain can be phosphorylated and can interact with intracellular signaling molecules
Cell adhesion molecules may also be linked to signaling pathways. What is the significance of this?
a cell may express different genes when bound to its identical neighbor
–> intracellular signaling molecules can lead to alteration of gene expression
At about the 8-cell stage of development, which adhesion molecule is first expressed in the embryo?
E-cadherin
- the cells change from being loosely attached, to a very compact ball (more stuck and morphed to each other, compaction)
- this may be the reason that twinning can no longer occur after about the 8-cell stage; the cells are too firmly attached
During early gastrulation, all cells of the ectodermal layer express which adhesion molecule?
E-cadherin
*when neural induction occurs, the future neural cells down-regulate E-cadherin and express N-cadherin
When neural induction occurs, the future neural cells down-regulate E-cadherin and express N-cadherin. Where are neural crest cells?
neural crest cells at ends of N-cadherin section
E-cadherin marks what cells? N-cadherin marks what cells?
E-cadhern marks ectodermal cells
N-cadherin marks neural cells
Initially all cells ofthe neural plate express N-cadherin. However, as the neural tube starts to close, the cells at the neural crest lose N-cadherin expression. What is the consequence for these cells?
they are now free to migrate
*neural crest cells that finally contribute to ganglia re-express N-cadherin, so that they can interact with other neural cells
Migrating neural crest cells express which cadherin?
neither
N-cadherin expression is found in the neural tube or ectoderm?
neural tube
*E-cadherin expressed in ectoderm
Remember, alterations in cell adhesion can lead to what?
changes in gene expression
Cells of the inner cell mass express what?
PE-CAM
*first, multiple independent cells in the blastocyst express PE-CAM. These cells move inside to form the ICM
What is intercalation?
- means to “insert between two others”
- this movement functions to elongate embryonic tissues and involves both cell movement and changes in cell adhesion
Ex: lengthening of the notochord along the cranio-caudal axis by intercalation
Describe the intercalation of the notochord
Initially it is fairly fat and disorganized, and then they become organized and a long, thin structure
Epithelial-Mesenchymal Transition (EMT)
- at a number of times during early development, cells lose their adhesive properties, leave a specific cell layer, and become migratory
i. e. they become mesenchymal - EMT is required for gastrulation, neural crest migration, and heart valve formation
What is EMT required for?
- gastrulation
- neural crest migration
- heart valve formation
What two transcription factors regulate the migratory phenotype?
snail and slug
Expression of snail and slug in tumors is associated with ________ (decreased/increased) EMT and metastasis.
increased
