Signaling pathways in

Development
 Induction
• Local interactions between cells,
mediated by secreted or cell-
surface signaling molecules by a
population of cells, to influence the
development of neighboring cells.
 Binary fate induction
• Induction could involve a binary
choice, one fate verses the other
fate or fail to develop.

X
With induction Without induction

A D
 Common signaling pathways
in development
• TGF-β/dpp
• Hedgehog
• Wnt/wingless
• Notch
• Receptor tyrosine kinase (RTK)
• Jak/STAT
• nuclear receptor
 Examples

Wnt

FGF5
EGF
TGF-β signaling
 Antagonistic effects between
Chordin and BMP4

Animal cap Epidermal tissue

Chordin
Neural tissue

Chordin
+ BMP4 Epidermal tissue
 What is the default fate?

Epidermal Neural
fate fate

Short range effect of BMP signaling

requires cell-cell interaction
Modulation of BMP4/Dpp activity
Conservation of the dorsoventral
patterning pathway

protease inhibitor signal

Fruit fly Tolloid Sog Dpp
Frog Xolloid Chordin BMP2/BMP4
Zebrafish Minifin Chordino Swirl
 Function of cholesterol
modification is to
spatially restrict the Hh
signal:

1. Unmodified Hh has
inductive activity
2. Modified Hh only
induces response in
the immediate
neighboring cells,
while unmodified Hh
induces response in
cells located more
than a cell diameter
away.
The Hh signaling pathway
The Drosophila wing blade
A

P
en
Hh organizes pattern in the
Drosophila wing

Anterior clone
Shh

Patterning the chick limb

Morphogen property of Shh
(sonic hedgehog)

Floor plate

notochord
 Morphogen-like Hh in the wing
Nuclear Ci

dpp
Ptc

Hh

Hh: red Hh: green

Ptc: blue
Dpp: green
Dpp: red
 The Hh pathway regulates target genes through
activator & repressor forms of Cubitus interruptus (Ci)

Beach (2004), Science

dpp
Ci155 ptc
(activator)
en

Ci75 dpp
(repressor) hh
Three states for Hh signaling
Hh signalling, stem cells and cancer

Nature Reviews Cancer

3, 903-911 (2003)
 Induction
• Induction can also induce different
responses at different concentrations,
therefore, resulting in a tissue
containing multiple cell types. Two
mechanisms can account for this, a
gradient model and a relay model.
Gradient model

signal

A B C
Relay model

Signal 1 Signal 2 Signal 3

A B C
Dpp relays Hh signaling to pattern wing discs
The Wnt
pathway
Early cell lineage in the
nematode C. elegans

mesoderm endoderm
Signal from P2
induces EMS
asymmetric division

Isolated EMS Contact with P2

EMS EMS P2

MS MS MS E
 mom1-5 (more
mesoderm)
wild type mom-
EMS EMS

MS E MS MS
mom1-3 are required in
the P2 cell, and mom4-
5 in the EMS cell. mom-
2: Wnt-2 and mom-5:
Frizzled receptor
Pop-1: TCF/Lef like, a repressor

endoderm 2x No 2x

Pop-1
staining

MS E
• Induction can be reciprocal between
two populations of cells that are
already different.

a b

A B
Hh and Wingless (Wg) act together
to define parasegment boundary in
Drosophila embryo
Cell-cell communication
The Notch pathway Delta

Notch γ-secretase

Su(H)
activation
repression
E(spl)

E(spl)
achaete, scute
 Notch signaling pathway leads to
downregulation of proneural genes
Asymmetric cell division and
Cell-cell communication

ES organ SOP

hair
IIA IIB

socket
g
sheath
neuron
so h
sh n
glia
 SOP Numb

Asymmetric localization

Notch

IIA IIB

Numb
Cell fate determination
FGFR signaling pathway in the Drosophila eye

Eye imaginal disc

Adult compound eye
Recruitment of photoreceptors
 Lineage

lacZ/+
P
lacZ/lacZ A B +/+

2 5 7 C

3 4
 Cell Recruitment

3
2 2
8 8 8
5 5
4
R7 is induced by R8
 R8

Boss

Sevenless

Ras/Raf seveless+ in R7 boss+ in R8

MAPK

R7
Default repression to keep local activator silenced
How signaling converts repression to activation?
 Habit #3: cooperative activation

Local activator: signal-independent,

restricted expression in specific territories