Cell-cell communication

One of the most critical times in a mammal’s life occurs soon after conception as the

Embryo passes from the oviduct (Fallopian tube) & enters the uterus

If development is to continue

The embryo must adhere to the uterine wall

The first differentiation event in mammalian development distinguishes the

Trophoblast cells from the inner cell mass

Trophoblast cells have Catherine that

Anchor them to the uterine wall

Cadherins (calcium dependent)

Primary cell adhesion molecules; tans membrane proteins that interact with other Catherine on adjacent cells

Migration is common feature for both

Epithelial and mesenchymal

In epithelia the motive force for migration is usually provided by

Cells at the edge of the sheet & the rest of the cells passively follow

In mesenchymal migration

Individual cells migrate through the extracellular matrix

Polarization

First stage of migration; where a cell defines its front and back

Polarization can be directed by

Signals from cells or from the extracellular matrix; these signals recognize the cytoskeleton so that the front part of the cell becomes structurally different from the back part

Protrusion of the cell’s leading edge

Second stage of migration; the mechanical force for protrusion is provided by the polymerization of actin microfilaments at the cell membrane, creating lamellipodia or filopodia

Lamellipodia

Sheet like extension containing a dense mesh of actin filaments

Filopodia

Stiff protrusions at the leading edge containing loose bundles of actin filaments

Adhesion of the cell to its extracellular substrate

Third stage of migration

Integrins

Proteins that span the cell membrane, connecting the extracellular matrix to the actin cytoskeleton

Fibronectin

A large glycoprotein that serves as a general adhesion molecule, linking cell to collagen and other substrates

Fourth stage of migration

Release of adhesions in the rear, allowing the cell to migrate in the forward direction

Fibroblast growth factors (FGF)

A family of paracrine factors

These factors can activate an intracellar pathway called

JAK-STAT cascade

JAK-STAT cascade

Important in the differentiation of blood cells, the growth of limbs, and milk production

Paracrine reaction

When proteins synthesized by one cell can diffuse over short distances to induce changes in neighboring cells

Tyrosine protein kinase

Enzyme that phosphorylation tyrosine side chains on intracellular proteins; activated when the protein (paracrine factor) binds to its receptor

The cascade begins with the binding of a growth factor to a

Receptor that is linked to JAK (Janus kinase) proteins

The kinases phosphorylate

STAT (signal transducers and activators of transcription) transcription factors

Phosphorylation STAT enters the nucleus and

Binds to it’s enhancers

The proteins of the hedgehog family of paracrine factors are often used by embryos to

Induce specific cell types and to create boundaries between tissues

Vertebrates have at least 3 homologues of the Drosophila hedgehog gene

Sonic hedgehog

Desert hedgehog

Indian hedgehog

Sonic hedgehog has the greatest number of

Developmental functions

Among other things it is responsible for assuring that

Motor neurons come only from the central portion of the neural tube and that our digits are always in the right place

juxtacrine signaling

Proteins of the inducing cell interact with receptor proteins of adjacent cells without actually diffusing from the inducing cell

Cells expressing the delta protein in their cell membranes can activate neighboring cells that

Contain notch proteins in their cell membranes

The cytoplasmic component of notch can enter the nucleus and bind to transcription factors, activating their target genes

This activation is thought to involve Huston acetyltransferases

Epithelial-mesenchymal transition (EMT) is an orderly series of events whereby epithelial cells are transformed into mesenchymal cells

In this transition, a stationary epithelial cell becomes a migratory mesenchymal cell that can invade tissues and form organs in new places

EMT is usually initiated when paracrine factors from neighboring cells activate gene expression in target cells,

Instructing those cells to down regulate cadherin production, rearrange their actin cytoskeletons, and secrete new matrix molecules characteristic of mesenchymal cells

EMT is critical in development because it is necessary for the formation of the neural crest cells from the dorsal most region of the neural tube,

The formation of mesoderm in chick embryos, and the formation of vertebrae precursors cells from the somites

EMT is also important in adults during the

Process of wound healing

The most critical adult form of EMT is seen in cancer metastasis

Cadherins are downregulated, the cytoskeleton is reorganized, and cancer cells secrete mesenchymal matrix proteins while undergoing cell division