This was my report during our developmental biology class. It includes Induction and competence, inducer molecule, signal transduction cascades,

2. CELL-CELL
COMMUNICATION IN
DEVELOPMENT
MUSLIMA P. LIWALUG

3. “The phenomenon of life itself
negates the boundaries that
customarily divide our disciplines
and fields.”
Hans Jonas (1996)

4. Cells develop in the context of their environment,
including:
o their immediate cellular neighborhood
o their tissue identity
o their position in the body
Developing cells receive signals from each other of
these location, and they, in turn, signal the cells
around them.

5. COMPONENTS OF SIGNAL/RESPONSE
SYSTEM MUST INCLUDE
 a signal
 a receptor to that signal
 a mechanism to translate and or transport the signal
 a mechanism to translate the signal to a stimulation
(or repression) of gene expression

6. CELL-CELL
COMMUNICATION
OVERVIEW

7. Induction and Competence
Paracrine Factors: The Inducer Molecule
Signal Transduction Cascades: The
Response to Inducers
Cell Death Pathways
Juxtacrine Signaling
Cross-Talk Between Pathways
Maintenance of the Differentiated State

8. INDUCTION &
COMPETENCE
How do cells and tissues “know” how to develop?

9. INDUCTION AND
COMPETENCE
Development depends on the precise arrangement of tissues and cells.
- organ construction is precisely coordinated in time and space
- arrangements of cells and tissues change over time
Induction – interaction at close range between two or more cells or tissues
with different histories and properties.
Inducer – tissue that produces a signal that changes cellular behavior
Responder – tissue being induced; the target tissue
NOTE: The target tissue must be capable of responding equal
Competence – the ability of a cell or tissue to respond to a specific inductive
signal

11. Lens placode (tissue thickening) – induce
head ectoderm by close contact with neural
(brain) tissue
The developing lens then includes brain to
form the optic cup.

12. INDUCTION AND COMPETENCE

13. INDUCTION AND COMPETENCE

14. INDUCERS
are molecular components
For example optic vesicle inducers:
o BMP4 (bone morphogenic protein 4)
- induces Sox2 and Sox3 transcription
factors
o FgF8 (fibroblast growth factor 8)
- induces L-Maf Transcription Factor

15. Competence
• ability of a cell or tissue to respond to a
specific inductive signal
• actively acquired (and can also be transient)
During lens induction Pax6 is expressed in the
head ectoderm, but not in the other regions of
the surface ectoderm.
Pax6 is a competence factor for lens induction.

16. STEPWISE INDUCTION
Inducer
Often multiple inducer tissues operate on a structure;
e.g. for frog lens:
1st inducer – pharyngeal endoderm & heart-forming
mesoderm
2nd inducer – anterior neural plate (including signal for
ectoderm Pax6 synthesis)

17. STEPWISE INDUCTION

18. RECIPROCAL INDUCTION

19. MOUSE LENS –
RECIPROCAL INDUCTION
Day 9 Mid-Day 9 Mid-Day 10 Mid-Day 11 Day 13

20. INDUCTIVE
INTERACTIONS
Interactions between epithelial and mesenchyme:
• mesenchyme plays an instructive role (as the inducing tissue)
• initiates gene activity in epithelial cells

21. INSTRUCTIVE AND
PERMISSIVE INTERACTIONS
INSTRUCTIVE:
A signal from the inducing cell is necessary for initiating new
gene expression in the responding cell.
For example, optic vesicle placed under new region of head ectoderm
- Without the inducing cell, the responding cell is not capable of
differentiating (in that particular way)
Instructive interactions restrict the cell’s developmental
options.

22. INSTRUCTIVE AND
PERMISSIVE INTERACTIONS
General Principles of Instructive Interactions:
1. In the presence of tissue A, responding tissue B develops in a
certain way.
2. In the absence of tissue A, responding tissue B does not develop in
that way.
3. In the absence of tissue A, but in the presence of tissue C, tissue B
does not develop in that way.

23. INSTRUCTIVE AND
PERMISSIVE INTERACTIONS
INSTRUCTIVE
- a signal from the inducing cell is necessary for initiating new
gene expression in the responding cell
PERMISSIVE
- the responding tissue has already been specified; needs only an
environment that allows the expression of those traits.
- permissive interactions tend to regulate the degree of expression
of the remaining developmental potential of the cell.

24. EPITHELIA &
MESENCHYME
Epithelia
- sheets or tubes of connected cells
- originate from any cell layer
Mesenchyme
- loosely packed, unconnected
- derived from mesoderm or neural crest
ALL ORGANS CONSIST OF AN EPITHELIUM AND
AN ASSOCIATED MESENCHYME

25. MESENCHYMAL-EPITHELIAL
INTERACTIONS
o many inductions involve interactions between
epithelia and mesenchyme
o mesenchyme initiates gene activity in epithelial
cells

26. SOME EPITHELIAL-
MESENCHYMAL INTERACTIONS
ORGAN EPITHELIAL COMPONENT MESENCHYMAL
COMPONENT
Cutaneous Structures
(hair, feather, sweat glans,
mammary glands)
Epidermis
(ectoderm)
Dermis
(mesoderm)
Limb Epidermis
(ectoderm)
Mesenchyme
(mesoderm)
Gut organs
(liver, pancreas, salivary
glands)
Epidermis
(endoderm)
Mesenchyme
(mesoderm)
Pharyngeal and Respiratory
associated organs
(lungs, thymus, thyroid)
Epithelium
(endoderm)
Mesenchyme
(mesoderm)
Kidney Ureteric bud epithelium
(mesoderm)
Mesenchyme
(mesoderm)
Tooth Jaw epithelium
(ectoderm)
Mesenchyme
(Neural Crest)

27. SKIN EPITHELIUM &
MESENCHYME
Epithelial
Derivatives:
• Hair
• Scales
• Feathers
• Mammary
glands
• Sweat
glands
Derivative
type
depends
on
restriction
by region
and
genetics

28. REGIONAL SPECIFICITY
REGIONAL SPECIFICITY - source of the mesenchyme (inducing
tissue) determines the structure of the epithelial derivative.

29. GENETIC SPECIFICITY OF
INDCUTION
Genetic specificity – epithelial response is limited to genomic
capability
Mesenchyme induces epithelial
structures…
…but can only induce what the
epithelium is genetically able to
produce.

30. PARACRINE FACTORS:
A TYPE OF INDUCER MOLECULE
Intracellular and intercellular signals.

31. SIGNAL TRANSDUCTION OR
SIGNAL TRANSDUCTION
CASCADES
o Response to signals at molecular level
o Signaling pathways gone bad – proto-oncogenes

32. INDUCING SIGNALS

33. INDUCING SIGNALS
Self-generatedCirculating
signal

34. PARACRINE FACTORS
Signaling molecules (proteins) produced by one cell
(tissue) and distributed via diffusion to a localized area;
often act as inducers.

35. PARACRINE FACTOR
FAMILIES
Fibroblast growth factor (FGF)
Hedgehog family
Wingless family (Wnt)
TGF-βsuperfamily (TGF = transforming growth factor)
• TGF-βfamily
• Activin family
• Bone morphogenic proteins (BMPs)
• Vg1 family

36. SIGNAL TRANSDUCTION
Extracellular signals are received at the membrane
and then transduced to the cytoplasm at the cell
membrane
- external signal is transmitted into the interior
of the cell

37. SIGNAL TRANSDUCTION
CASCADE
omost intercellular and intracellular signals are part of larger
sets of pathways signal transduction cascades
o activated products or intermediates trigger other pathways
e.g. receptor tyrosine kinase (RTK)
(kinase = enzyme that phosphorylates a protein)

38. SIGNAL TRANSDUCTION
Receptor Tyrosine Kinase (RTK)

39. RTK PATHWAY - GENERIC

40. JAK-STAT PATHWAY
JAK (Janus kinase)
- non-receptor tyrosine kinase
STAT (Signal Transducers and Activators of Transcription)
- transcription factor
Pathway activators:
o prolactin, cytokines, growth hormones
ocell proliferation
odifferentiation
oapoptosis
NOTE: STATs can be
activated independently of
JAKs
• RTK; e.g. EGF receptor
• non-receptor tyrosine
kinases; e.g. c-src

41. JAK-STAT PATHWAY

42. HEDGEHOG PATHWAY -
GENERIC

43. WNT PATHWAY
APC - adenomatosis polyposis coli (tumor suppressor)
- targets -catenin for degradation
GSK-3 - Glycogen synthase kinase 3
- prevents -catenin dissociation from APC
Wnt binds to Frizzled receptor family
- activates Disheveled
- Disheveled blocks GSK-3
- beta-catenin released from APC
- enters nucleus
- associates with LEF/TCF TFs

44. WNT PATHWAYS

45. SMAD PATHWAY

46. PROTO-ONCOGENES

47. JUXTACRINE
SIGNALING OR
EXTRACELLULAR
MATRIX SIGNALING

48. JUXTACRINE SIGNALING
Proteins from the inducing cell
interact with receptors from
adjacent responding cells
without diffusing from the cell
producing them

49. NOTCH PATHWAY
1. Delta binds Notch
2. Binding activates proteolytic
cleavage of Notch inner
portion
3. Proteolytic fragment moves
to nucleus
• Displaces repressor
• Recruits p300 HAT
• Activates transcription

50. EXTRACELLULAR MATRIX
SIGNALS
EMC - macromolecules secreted by cells into
their immediate environment
- macromolecules form a region of non-cellular
material between the cells
- cell adhesion, migration, formation of epithelial
sheets and tubes
- collagen, proteoglycans (fibronectin, laminin)

51. CROSS-TALK

52. CROSS-TALK

53. CROSS-TALK
Signal transduction is often not a
linear event
e.g.
 cascades
 multiple signals required
 multiple products required
also:
 inhibitory signals
 promiscuous signals/receptors
Cross-talk provides opportunities
for emergent properties;
e.g.
 hypersensitivity
 stability
 bistability

54. CELL DEATH
PATHWAYS

55. APOPTOSIS
- programmed cell death
Developmental:
- embryonic neural growth
- embryonic brain produces 3X neurons found at
birth
- hand and foot
- webbing between digits
- teeth
- middle ear space
- vaginal opening
- male mammary tissue
- frog tails (at metamorphosis)
Adult:
-most cells and tissues

56. APOPTOSIS SIGNALS
Paracrine –e.g. BMP4 (connective tissues, frog
ectoderm, tooth primordia), JAK-STAT,
Hedgehog
Pre-programming: some cells will die unless
“rescued”; e.g. mammalian
RBCs rescued by erythropoietin (hormone;
activates JAK-STAT)
Mechanism – caspases (proteases) – cause
autodigestion of the cell.

57. MAINTAINING
DIFFERENTIATION
How to ensure that a tissue remains stable.

58. MAINTAINING
DIFFERENTIATION - 1
1. Activating signal
initiates production of a
transcription factor
which stimulates
transcription of its own
gene.

59. MAINTAINING
DIFFERENTIATION - 2
2) Synthesized
proteins act to
stabilize chromatin to
keep gene accessible.

60. MAINTAINING
DIFFERENTIATION - 3
3) Autocrine signaling:
same cell makes signaling
molecule and receptor.
Community effect - the
exchange of signals among
equivalent
cells stabilizes the same
determined state for all of
them.

61. MAINTAINING
DIFFERENTIATION - 4
4) Paracrine loop -
interaction with
neighboring cells
such that each
stimulates
differentiation of the
other.

62. EIGHT EDITION
REFERENCE
SC O T T F. GI L B E RT

64. SUMMARY
Cell-Cell Communication

65. SUMMARY
1. Inductive interactions involve inducing and responding tissues.
2. The ability to respond to inductive signals depends upon the
competence of the responding cells.
3. Reciprocal induction occurs when the two interacting tissues are both
inducers and are competent to respond each other’s signals.
4. Cascades of inductive events are responsible for organ formation.
5. Regionally specific inductions can generate different structures from
the same responding tissue.
6. The specific response to an inducer is determined by the genome of
the responding tissue.

66. SUMMARY
7. Paracrine interactions occur when a cell or tissue secretes proteins
that induce changes in neighboring cells. Juxtacrine interactions are
inductive interactions that take place between the cell membranes of
adjacent cells or between a cell membrane and an extracellular
matrix secreted by another cell.
8. Paracrine factors are proteins secreted by inducing cells. These
factors bind to cell membrane receptors in competent responding
cells.
9. Competent cells respond to paracrine factors through signal
transduction pathways. Competence is the ability to bind and to
respond to the inducers, and it is often the result of a prior induction.

67. SUMMARY
10. Signal transduction pathways begin with a paracrine or juxtacrine
factor causing a conformational change in its cell membrane receptor.
The new shapes results in enzymatic activity in the cytoplasmic
domain of the receptor protein. This activity allows the receptor to
phosphorylate other cytoplasmic proteins. Eventually, a cascade of
such reactions activates a transcription factor (or set of factors) that
activates or represses specific gene activity.
11. Programmed cell death is one possible response to inductive stimuli.
Apoptosis is a critical part of life.
12. Gap junctions allow ions and small molecules to move between cells
and facilitate coordinated action of coupled cells.

68. SUMMARY
13. There is cross-talk between signal transduction pathways, which
allows the cell to respond to multiple inputs simultaneously.
14. The maintenance of the differentiated state can be accomplished by
positive feedback loops involving transcription factors, autocrine
factors, or paracrine factors.