Cell to Cell Communication

Question 1

how do cells and tissues “know” how to develop

Answer 1

induction and competence

Question 2

• proteins made by a cell or group of cells that alter the behavior and differentiation of adjacent
• inter- and intracellular signals

Answer 2

paracrine factors

Question 3

response to signals at the molecular level

Answer 3

signal transduction/ signal transduction cascades

Question 4

communication between cells requires (2)

Answer 4

• ligand
• receptor protein

Question 5

the signaling molecule

Answer 5

ligand

Question 6

the molecule to which the receptor binds; maybe on the plasma membrane or within the cell

Answer 6

receptor protein

Question 7

types of cell signaling (4) - depending on how far

1. ________: cell targets itself
2. ________: short distance
3. ________: long distance
   4: ________: gap junction

Answer 7

1. autocrine signaling
2. paracrine signaling
3. endocrine signaling
4. juxtacrine/direct signaling

Question 8

Types of binding
1. ________ - identical receptor or adhesion molecule
2. ________- different receptor or adhesion molecule

Answer 8

1. homophilic
2. heterophilic

Question 9

Types of receptors (2)

1. __________: within the cell (cytoplasm) and respond to hydrophobic ligand molecules (ex: steroid hormones)
2. __________: integral proteins (at membrane) that bind to external signaling molecules and perform signal transduction. hydrophilic ligand molecules

Answer 9

1. Internal receptor (intracellular or cytoplasmic receptors)
2. Cell-surface receptors (transmembrane receptor)

Question 10

Receptor types (3 subclasses of cell-surface receptors)

1. __________: ion channel that opens in response to a ligand (ex: Na channel)
2. __________: receptor is an enzyme that is activated by the ligand
3. _________: a G-protein (bound to GTP) assists in transmitting the signal

Answer 10

1. channel linked receptors
2. enzymatic receptors
3. G protein-coupled receptor

Question 11

Three stages of signal transduction

1. _________ of extracellular signal
2. ________ of signal from outside of cell to inside of cell-often multi stepped
3. __________. Is initiated and/or occurs entirely within receiving cell

Answer 11

1. reception
2. transduction
3. cellular response

Question 12

• interaction at close range between two or more cell tissues with different histories and properties
• has two parts:

Answer 12

1. induction
   
   • inducer
   • responder

Question 13

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

Answer 13

inducer

Question 14

tissue being induced; the target tissue

Answer 14

responder

Question 15

• the ability of a cell or tissue to respond to a specific inductive signal (Waddington 1940)
• actively acquired (and can also be transient)

Answer 15

competence

Question 16

Induction - Vertebrate Eye Development

1. ______ are outgrowings of the brain which make contact with the ___________ and this contact induces changes necessary for futher development of the eye
2. _____________ ( tissue thickening) induced in head ectoderm by close contact with neural (brain) tissue.
3. The developing lens then induces brain to form the ________ (will develop into the pigmented retina and neural retina).

Answer 16

1. optic vesicles, surface ectoderm
2. lens placode
3. optic cup

Question 17

needed for normal induction of lens (2)

Answer 17

• presence of optical vesicle
• ectodermal competence

Question 18

Factors that enable a cell or tissue to respond to an inductive signal. These can be actively acquired and may be transient.

Answer 18

Competence factor

Question 19

**Competence factor **

• is a competence factor for lens inductions
• its expressed in the head ectoderm, but not in other regions of surface ectoderm.
• is needed for the surface ectoderm to respond to the inductive signal from the optic vesicles; the inducing tissue does not need it

Answer 19

Pax6

Question 20

When Pax6 is not wild-type and is a mutant, which is the defective component- the optic vesicle or the surface ectoderm?

Answer 20

surface ectoderm

Question 21

Studies in amphibians suggest that the first inducers maybe the ___________ and ___________________ that underlie the lens-forming ectoderm during the early and mid-gastrula stages.

Answer 21

pharyngeal endoderm and heart-forming mesoderm

Question 22

There is no single inducer of the lens.

Optical vesicle inducers: (2)

Answer 22

1. BMP4 (bone morphogenic protein 4)
2. Fgf8 (fibrobast growth factor 8)

Question 23

induces Sox2 and Sox3 transcription factos

Answer 23

BMP4 (bone morphogenic protein 4)

Question 24

induces L-maf transcription factor

Answer 24

Fgf8 (fibrobast growth factor 8)

Question 25

The combination of ______, ______, ______and ______ in the ectoderm ensures the production of the lens and the activation of lens-specific genes such as ________.

Answer 25

Pax6, Sox2, Sox3 and L-maf crystallin

Question 26

EFFECTS OF MULTIPLE INDUCERS (2)

Answer 26

1. Sequential and Additive 2. Reciprocal and Sequential Inductive Events

Question 27

example of Sequential and Additive (Inducers in Frog Lens Development) First Inducer: (2) Second Inducer: (1)

Answer 27

Pharyngeal Endoderm and Heart-Forming Mesoderm Anterior Neural Plate

Question 28

example of Reciprocal and Sequential Inductive Events

Answer 28

Vertebrate Eye Development

Question 29

Inductive interactions - ____________ plays an instructive role (as the inducing tissue) - initiates gene activity in ________ cells

Answer 29

- mesenchyme - epithelial

Question 30

The lens placode __________ by inducing the optic vesicle before the lens forms its characteristics fibers.

Answer 30

reciprocrates

Question 31

How do these interactions work? * _________ - a signal from the **inducer is required** for initiation new gene expression. Without the inducer, the cell is not capable of differentiating. * _________ -the tissue has already been specified, but requires an **environmental change** that allows expression of the differentiated tissues traits. (ex: many tissues need a solid substrate containing fibronectin in order to develop.)

Answer 31

* instructive interaction * permissive interaction

Question 32

All organs consist of an epithelium and an associated mesenchyme. Many inductions involve interactions between epithelia and mesenchyme. ___________ - sheets or tubes of connected cells - originate from any germ layer _________ - loosely packed, unconnected cells - derived from mesoderm or neural crest

Answer 32

epithelia mesenchyme

Question 33

Two types of specificity of induction ______ - source of mesenchyme (inducing tissue) determines the structure of the epithelial derivative; skin epithelium and mesenchyme ______ - epithelial response is limited to genomic capability (ex. _____ - a single organism that's made up of cells from two or more individuals (2 sets of DNA))

Answer 33

regional specificity genomic specificity - (ex: chimeras)

Question 34

_________: The Inducer Molecules _____________- signaling molecules (proteins) produced by one cell (tissue) and distributed via diffusion to a localized areal often act as inducers

Answer 34

Paracrine Factors Paracrine Factors / Growth and Differentiation Factors (GDF)

Question 35

Paracrine Factor Families (4)

Answer 35

1. Fibroblast growth factor (FGF) 2. Hedgehog family 3. Wingless family (Wnt) 4. TGF-β superfamily (Transforming growth factor) - TGF-β family - Activin family - Bone morphogenic proteins (BMPs) - Vg1 family

Question 36

Cell-Cell Communication * A cell's response to a signal often involves activating or inactivating proteins. * ______ is a common way to change the activity of a protein 1. _________- an enzyme that adds a phosphate to a protein 2. ________- an zyme that removes a phosphate from protein

Answer 36

* Phosphorylation 1. protein kinase 2. phosphatase

Question 37

Signal Transduction Pathways

Answer 37

1. RTK Pathway - Generic 2. JAK-STAT Pathway 3. Hedgehog pathway 4. Wnt signaling pathway/Beta-catenin pathway 5.The Notch pathway

Question 38

- active during development - repressed/silenced in adult - cause tumor formation when inappropriately activated = mutation (e.g. constitutive activation) > many cancers have mutated ______ Give 4 examples of this in RTK Pathway.

Answer 38

proto-oncogenes (onco = cancer) 1. RAS 2. RAF 3. MEK 4. ERK

Question 39

The _____________ is critical in numerous developmental processes. In the migrating neural crest cells of humans and mice, the pathway is important in activation the ________________ to produce pigment cells (melanoblast cells, pigmented retina).

Answer 39

micropthalmia transcription factor (Mitf)

Question 40

In JAK-STAT pathway > _______ - non-receptor tyrosine kinase > _______ - family transcription factor Note: STATs can be activated independently of JAKs - RTK - non receptor tyrosine kinases

Answer 40

Janus Kinase Signal Transduction and Activation of Transcription

Question 41

______ pathway is very important in regulation of human fetal bone growth. Mutation -> severe forms of dwarfism

Answer 41

(JAK-) STAT pathway

Question 42

_________ pathway is extremely important in vertebrate limb and neural differentiation.

Answer 42

Hedgehog pathway

Question 43

One remarkable feature of Hedgehog signal transduction pathway is the importance of ______. 1. It is critical for the catalytic cleavage of ________ protein. Only the AMINO TERMINAL PORTION is functional and secreted. It binds to the active N-terminus of the protein and allows this paracrine factor to diffuse over a range of a few hundred micrometer (**cholesterol modification**) 2. The ________ protein that binds sonic hedgehog also needs cholesterol in order to function.

Answer 43

Cholesterol 1. Sonic hedgehog protein 2. Patched protein

Question 44

Vertebrates have at least three homologues of the Drosophila hedgehog gene (3) * ________ - sertoli cells of the testes * ________ - gut and cartilage * ________ - important in embryo development

Answer 44

* desert hedgehog (dhh) * indian hedgehog (ihh) * sonic hedgehog (shh)

Question 45

* their name is a fusion of the name of the Drosophila segment polarity gene _______ with the name of its vertebrate homologues, _________. * they are a family of cysteine-rich glycoproteins * ___ gene family - ____ genes characterized in vertebrates and invertebrate combined - ____ in human * **Receptors**: __________ - _____ genes found in vertebrates

Answer 45

Wnt (Wingless-related integration site) Family - wingless, integrated - Wnt: 30, 19 - Frizzled gene family: 10

Question 46

The Wnt Signaling Pathway * ________: active in inducing the **dorsal cells of the somites to become muscle** and is involved in the specification of the midbrain cells * ________: critical in establishing the polarity of the insect and vertebrate limbs, promoting the proliferation of stem cells * _____ proteins play several roles in the development of the urogenital organs * ____ is necessary for kidney development and for **female sex determination**

Answer 46

Wnt1 Wnt proteins Wnt proteins Wnt4

Question 47

Wnt/Beta-catenin Pathway __________ - targets Beta-catenin for degradation __________ - prevents Beta-catenin from APC

Answer 47

APC (adenomatosis polyposis coli) GSK-3 (Glycogen synthase kinase 30

Question 48

____ pathway - important in development and homeostasis > cellular proliferation, differentiation, and apoptosis - involved in development of **sensosry hair cells** and **branched arterial networks** - associated with tissue growth and cancer, and cell death and tumor suppression - 4 NOTCH receptors in Mammals: (4) - Ligands: > Jagged protein family (2) > Delta-like protein family (3)

Answer 48

Notch Signaling Pathway - 4 NOTCH receptors in Mammals: (NOTCH1,NOTCH2...) - Ligands: > Jagged protein family (2): JAG1 and JAG2 > Delta-like protein family (3): DLL1, DLL3, and DLL4