PROXIMATE TISSUE INDUCTION

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• There will be translation of mRNA which will result to
Outline: a protein
I. Modes of Interaction
a. Signal Transduction Mechanism
b. Embryonic Induction Embryonic Induction
c. Intercellular SIgnals • Proximal Interaction - one group of cells changing the
II. Epithelio-Mesenchymal Interaction
behavior of an adjacent set of cells ! change in
a. Properties
b. Secondary Induction shape, mitotic rate, or fate.
III. Hormonal Mediation • Other changes:
PROXIMATE TISSUE INDUCTION changes in cell pathway, cell migration, synthesis of
certain molecules
PROXIMATE TISSUE INDUCTION
Components:
Induction - initiated by the Spemann organizer, which is in 1. Inducer - tissue which releases the signal/s
turn induced by the Nieuwkoop center. 2. Responder - tissue being induced (late cleavage)
Proximate Tissue Induction or Secondary Induction via nature
of the proximity of the cells Requirements in induction:
1. Modes of Interaction 1. Competence of RT
2. Epithelio-Mesenchymal Induction a. + receptor to bind signal
3. Hormonal Mediation b. + enzyme to form functional receptor
c. Repression of the inhibitor for transcription of the
MODES OF INTERACTION molecule
Signal Transduction Mechanism e.g. For the inhibitor GSK blocking the activation
of B-catenin, presence of Wnt represses GSK

Competence and Receptors

1. Reception
• Signal molecule reaches the target cell.
• Signal molecule or the means of inducing can be a 1. Normal
hormone which is diffusible and can reach the target 2. Different site though same ectoderm
cell. 3. Inducer is removed.
• The signal transduction shown is the typical one 4. Inducer is replaced.
(protein hormone), different from the case of
signalling from a steroid hormone. CONCLUSION: Induction occurs at the right space (or site)
2. Transduction and time.
• The signal will be transduced or transformed into a
message understood by the cell. 2. Paracrine Factors (Growth Factors/Differentiation Factors)
• Involves a cascade of events involving a wide array of • soluble/diffusible molecule release into extracellular
molecules and conformational changes in these space to influence nearby cells.
molecules, turning the signal into something that is • “Tool kits” in the development of the heart, kidney,
understood by the cell. eye, & teeth in all animals.
3. Response
• Eventually decided by the nucleus. Chemical Signals
1. Autocrine - release molecules and activate cells of the
• Assuming all the essential components are present,
same kind; self-induced.
the activation of genes will result to a proper
• E.g. T-helper cells (activate themselves)
response to that particular signal.

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2. Paracrine - nearby or adjacent cells; growth factors with a
small intervening space between two interacting cells
• Myoneural junctions - gap between neurons and a
muscle (neuromuscular junctions); release of
neurotransmitters like acetylcholine to activate the
target cells require that these pass through the
synaptic cleft

3. Juxtacrine - direct contact between two interacting cells;

cell membrane proteins on one cell interact with receptor
proteins on the adjacent cell
• Exemplified by Wnt and Hedgehog interactions

4. Endocrine - for long distance interactions; differs from

Paracrine in that gactors will be delivered through the
blood stream
• E. g. Pituitary gland hormones

Intercellular Signals
Quotable quote from Kuya Dennis: “Memorize yan.
Kailangang imemorize yan.” See Appendix

EPITHELIO-MESENCHYMAL INTERACTIONS

Properties of Epithelio-Mesenchymal Interactions

/* Much is from Gilbert din */

• Combination of experiments using excised portions
of the embryo
• Mesenchyme cell - derived from mesoderm or neural
crest cells (migrating); responsible for specificity of
induction in the competent ectoderm. Ectoderm
develops according to region from which mesoderm
was taken.
• Epidermal cells is derived from the three germ layers
o Endoderm of respiratory tissues are epithelial since
they are tightly packed cells resting on a basement
membrane
• Example given by Ma’am
o Skin is composed of two main tissues: an outer
epidermis (ectoderm) and a dermis (mesenchymal
tissue derived from the mesoderm).
o The chick epidermis signals the underlying dermal
cells to form condensations (probably by SHH and
TGF-β 2 proteins) and the condensed dermal
mesenchyme responds by secreting factors that
cause the epidermis to form regionally specific
cutaneous structures. These can be broad feathers
of the wing, the narrow feathers of the thigh, or the
scales and claws of the feet.
o The dermal mesenchyme is responsible for the
regional specificity of induction in the competent
epidermal epithelium. The epithelium develops
A. Regional Specificity of Induction cutaneous structures according to the region
from which the mesenchyme was taken. The
Regional specificity of induction in the chick – When cells from mesenchyme calls into play different sets of genes
different regions of the dermis (mesenchyme) are recombined in the responding epithelial cells.
with the epidermis (epithelium), the type of cutaneous
• The final fate of the structures produced by the
structure made by the epidermal epithelium is determined by
responding tissue will be dependent upon its source
the original source of the mesenchyme.

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• Regional specificity of induction is critical during
development of the digestive and respiratory systems Secondary Induction
o During morphogenesis of endodermal tubes,
endodermal epithelium respond differently to
different regionally specific mesenchymes →
esophagus, stomach, small intestine, colon,
bifurcation of trachea into right and left bronchi
which undergo repeated bifurcation into secondary
bronchioles inside the lungs until terminal bronchi
(bronchioles) → alveoli

B. Genetic Specificity of Induction

• Whereas the mesenchyme may instruct the
epithelium as to what genes to activate, the
responding epithelium can comply with these
instructions only so far as its genome permits
• According to Gilbert, this experiment was done by
Hans Spemann and Oscar Schotté
o Flank ectoderm was transplanted from an early
frog gastrula to the region of a newt gastrula • All inductions are instructive YET the response is
destined to become parts of the mouth and vice- selective.
versa • Response or fate is selective depending on the
o The mouth of a salamander has club-shaped competence of the cell.
balancers beneath its mouth, whereas the frog • Competence
tadpole produces mucus-secreting glands and 1. The current state of the Responding cell –
suckers. The frog tadpole also has a horny jaw presence of receptor, TM, TF, & repressor
without teeth, whereas the salamander has a set of 2. Developmental history of the cell –
calcareous teeth in its jaw. undifferentiated or differentiated.
o The results had salamander larvae with frog-like • Potential fate is greater than its prospective fate.
mouths and frog tadpoles with salamander teeth • “Selective Gene Expression from the same nuclear
and balancers. repertoire.”
o The mesodermal cells instructed the ectoderm to o Different responses of the responder directed or
make a mouth, but the ectoderm responded by depended upon the different sets of gene
making the only kind of mouth it knew how to products or gene products that are present in
make, no matter how inappropriate. the cell. The kind of the cell is similarly important.
Final response would depend on the machinery
and the timeframe (at what point will it be most
receptive).

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Timeline
• Within a certain time frame; sequential and synchronous;
presence of crosslinking of messages

• As early as late gastrula, there are signals released to the

prospective ectoderm to become neural ectoderm (neural
plate stage – cuboidal -> columnar) and to the neural
tube.
! complete array of molecules for maturation

In addition to the gene products, there are hormones that are

important in the development:

INTRODUCTION TO HORMONAL MEDIATION

1. Starting point of mammary cord proliferation.

a. Increase in rate of mitosis in epithelial cells induced
Sequential induction in Eye Development
by mesenchymal cells (highly undifferentiated and loosely
• Graph: Cleavage only has rapid cell division. The graph
arranged)
shows that the cells increase rapidly. Gastrula is the start
b. Rapid cell proliferation -> invagination -> mammary
of differentiation. The newly proliferated cells undergo
cord
change of shapes: convergent extension, radial
c. Mammary cord is the aggregation of cells.
intercalation by the deep involuting marginal zone cells,
2. Mammary gland - nipple (opens to most anterior part)
etc.
and duct (opens to most posterior part)
• Midgastrula to late neurula
3. Ductal growth - ramification/branching (repeated
o · Most receptive and competent cells both in time
bifurcation)
and capacity
4. Repeated bifurcation and development of secretory
o · Peaks, focused on the organ rudiment formation,
cells (determined to produce milk casein)
beginning with the neural tube formation.

Epithelio – mesenchymal induction

From 2018:
• Graph shows the response in the head ectoderm ->
placode, vesicle -> fibers
• Lens fibers formation begins in actual change in
morphology and synthesis of luxury protein,
crystalline.
o 3 or 4 interactions with adjacent cells for
complex induction.
o E.g. Somites – from notochord, lateral plate
mesoderm, ectoderm
o Absence of 1 or 2 factors – delay in
development/abnormalities

See Appendix Special notes:

1. Prolactin comes from the anterior pituitary gland
1. Head ectoderm transformed to lens placode by optic 2. Oxytocin is in charge of the release of milk; also in
vesicle – change in morphology, elongates; charge of the uterine contractions (from the posterior
invaginates. Change in shape of epithelium to pituitary)
columnar (thickening). 3. Oxytocin is triggered by the sucking of the infant
2. Lens placode induces optic vesicle to become optic
cup. END
3. Lens placode becomes lens vesicle (induced by the David. Raymond.
optic cup). Anna for formatting.
4. Lens vesicle induces optic cup into sensory and
pigmented epithelium. “You cannot escape the responsibility of tomorrow by
5. Lens vesicle will induce the overlying ectoderm to evading it today.”
become the cornea.
• There is a sequential as well as synchronous
induction from the lens vesicle to the optic
vesicle and vice versa.

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APPENDIX
For interrelated networks of information (go HPED!), look at Gilbert

Family of Proteins Receptor Roles in Development

(products of differential gene or RNA splicing)

Fibroblast growth factors Tyrosine Kinases Angiogenesis, axon and muscle development
10 Mammalian FGFs

Epidermal growth factors EGF Receptor Insect eye

Transforming growth factor (TGF-β) e. g. Activin, Vg1, BMPs, Serine-threonine Mesoderm induction in Xenopus
MIH, and Nodal (host of different protein molecules important protein kinase Patterning of Dorso-Ventral Axis
for patterning the DV axis like ventralizing effect by BMPs or Synthesis of collagen and fibronectin, ducts in
dorsalizing effect chordins etc.) Nodal is for left-right asymmetry liver, kidney and salivary glands

Hedgehog in insects, Sonic HedgeHog, Desert HedgeHog, Patched Positional signal in Vertebrate Limb and
Indian HedgeHog (galing sa Notochord influencing the Neural Neural Tube, R-L asymmetry
Tube) activated after Nodal for the L-R Asymmetry

Wingless (Wnt) was discovered in Drosophila wingless gene Frizzled DV axis in Xenopus
Polarity of insect and vertebrate limbs

Integrate in vertebrates Active in inducing somites to become muscles

Delta and Serrate Notch Inhibitory signal in Notch Signaling

Ephrins Ephrin receptors Vertebrate Nervous systems

*Note ephrins and semaphorins are necessary for segmentation pattern
in vertebrates.

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