Lecture 6 Developmental and Human Embryology exam 2

ECM as a source of developmental signals

- cell to cell interactions do not happen in the absence of an environment; occur in coordination with and often due to the environmental conditions surrounding the cells.

extracellular matrix

a insoluble network consisting of macromolecules secreted by cells into their environment

ECM contains

collagen, proteoglycans specialized glycoproteins (laminins and fibronectins)

basal lamina

ECM consisting of collagen IV and laminin

cell adhesion, migration and the formation of epithelial sheets/tubes all require

require the ECM attachment!!

integrin receptors

bind ECM molecules

Epithelial-mesenchymal transition (EMT)

- EMT is an orderly series of events whereby epithelial cells are transformed into mesenchymal cells

- EMT integrates many of topics discusses so far

- Can form types of cancer

Cell Signaling

- cell differentiation and behavior are regulated by signals from one cell being received by another

- cells change the behavior of adjacent or nearby cells causing them to change shape, mitotic rate, or cell fate.

induction

this interaction at close range between 2 or more cells or tissues of different histories

- paracrine signaling

- juxtacrine signaling

cell signaling - 2 components to an inductive signal

1. Inducer

2. Responder

Inducer =

tissue that produces the signal that changes the cellular behavior of the tissue.

paracrine factor of the inducer

proteins made by a cell or group of cells that alter the behavior/differentiation of the neighboring/adjacent cells.

Responder =

is the tissue being induced. contain a receptor for the inducing factor. need to have the proper receptor to get the proper signal.

competence

the ability to respond to an inductive signal

reciprocal inductions

the responding tissue becomes an inducer and induces the inducer (would now be a responder) Look at slide 21

cell signaling - 2 major modes of inductive interactions

1. instructive interaction

2. permissive interaction

instructive interaction

a signal from an inducing cell is necessary for initiating a new gene expression in the responding cell.

Permissive interaction

the responding tissue has already been specified and needs only an environment that allows the expression of these traits

types of inducer molecules

1. juxtacrine

2. paracrine

3. autocrine

4. endocrine

juxtacrine

cell membrane proteins on one cell surface interact with the receptor proteins on the adjacent cell surfaces

paracrine

proteins synthesized by one cell are secreted and diffuse over short distances to induce neighboring cells

autocrine

a factor secreted by a cell acts on the same cell that released the factor

endocrine

factors that travel through the blood to exert their effects (hormones)

paracrine molecules as morphogens

- one of the most important mechanisms governing cell fate specification involves gradients of paracrine factors that regulate gene expression = morphogen

morphogen =

a diffusible biochemical molecule that can determine the fate of a cell by its concentration

response to paracrine factors

- the induction of numerous organs is controlled by a relatively small set of paracrine factors

most paracrine factors are grouped into 1 of 4 major families:

1. FGF - fiber glass

2. Hedgehog

3. Wnt - wingless

4. TGF-B - transforming

paracrine factors work by

binding receptors and setting off a cascade of enyzmatic reactions that lead to regulation of transcription factors or cytoskeleton. aka signal transduction cascades

kinases:

an enzyme (protein) that catalyzes the transfer of phosphate group from ATP to specific molecule or protein.

- phosphorylated protein creates additional function (activation)

receptor tyrosine kinase =

the receptor is a kinase

FGF factors and the RTK pathway

- FGF are paracrine factors. 2 dozen structurally related members.

- FGF genes can produce many isoforms

- FGFs work by binding FGFRs (receptors)

= Fgf8 is important in limb and lens development

FGFRs are RTKs and work through

signal cascades

- Ras pathway

- Jak-Stat pathway

Hedgehog family

- vertebrates have 3 homologs to the fly: Shh. Dhh, Ihh

- Shh has the greatest function in development

Wnt family

- at least 15 members; many functions

- mash of fly wingless - integrated genes

- "canonical" or "non-canonical"

TGF-B Superfamily

- more than 30 structurally related members

juxtacrine signaling

- 2 most widely used juxtacrine factors are notch and eph receptors.

- notch - binds delta jagged or serrate

- eph receptors - binds ephrin ligands