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Morphogen gradient, cascade, signal transduction. Maternal effect genes. Zygotic genes Syncytial blastoderm. Cellular blastoderm. Homeotic selector genes Similar signal into different structures— Different interpretation—controlled by Hox genes. Metamorphosis.

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morphogen gradient cascade signal transduction
Morphogen gradient, cascade, signal transduction

Maternal effect genes

Zygotic genes

Syncytial blastoderm

Cellular blastoderm

slide2

Homeotic selector genes

Similar signal into different structures—

Different interpretation—controlled by Hox genes

homeotic transformation of the wing and haltere
Homeotic transformation of the wing and haltere

Homeotic genes—mutated into

homeosis transformation

As positional identity specifiers

Mutant-antennapedia—into leg

Bithorax-haltere into wing

imaginal discs and adult thoracic appendages
Imaginal discs and adult thoracic appendages

Bithorax mutation—Ubx misexpressed

T3 into T2 –anterior haltere into

Anterior wing

Postbithorax muation (pbx)—

Regulatory region of the Ubx—

Posterior of the haltere into wing

homeotic selector genes
Homeotic selector genes

Each segment unique identity—master regulator genes

Homeotic selector genes—control other genes-required

throughout development

Fig. 5-37

Spatial& temporal expression—mechanism of controlling of these genes

the spatial pattern of expression of genes of the bithorax complex
The spatial pattern of expression of genes of the bithorax complex

Bithorax—Ultrabithorax –5-12

Abdominal-A—7-13

Abdominal-B—10-13

Bithorax mutant –PS 4 default state

Fig. 5-39

slide9

Bithorax mutant –PS 4 default state

+Ubx—5,6

+Abd-A—7,8,9

+Abd-B—10

Combinatorial manner

Lack Ubx—5,6 to 4

also 7-14 thorax structure in the abdomen

Hox—gap, pair-rule for the first 4 hours,

then polycomb (repression), and Trithorax (activation)

Fig. 5-39

segmental identity of imaginal disc
Segmental identity of imaginal disc

Antennapedia—expressed in legs, but not in antenna

If in head, antennae into legs

Hth (homothorax) and Dll (distal-less)—expressed in antennae and leg

In antenna: as selector to specify antenna

In leg: antennapedia prevents Hth and Dll acting together

Dominant antennapedia mutant (gene on)—

blocks Hth and Dll in antennae disc, so leg forms

No Hth, antenna into leg

slide11

Gene expression in the visceral mesoderm

patterns the underlying gut endoderm

Patterning of the endoderm

Labial—antennapedia complex

Fig. 5-40

slide17

Mutation in HoxD13—synpolydactyly

Extra digits & interphalangeal webbing (hetero)

Similar but more severe & bony malformation

of hands, wrists (Homo)

slide18

Anterior/posterior extremities

Terminal structure-

acron., telson,

most posterior abdominal segment

Torso---receptor tyrosine kinase

Ligand---trunk

Before fertilization ligand immobilized

Small quantities—

bound to torso at the poles

little left to diffuse

Fig. 5-7

slide19

Torso signaling

Groucho: repressor

Huckenbein, tailless are released

from transcriptional suppression

signals from older to younger egg chambers
Signals from older to younger egg chambers

Red arrow: Delta-Notch induces anterior polar follicle cells

JAK-STAT: form the stalk cells

Yellow arrow: signals induce E-cadherins expression

slide22

A/P Determination during oogenesis

The oocyte move towards one

end in contact with follicle cells

Both the oocyte and the posterior

follicle cells express high levels

of the E-cadherin

If E-cadherin is removed,

the oocyte is randomly positioned.

Then the oocyte induces surrounding

follicle cell to adopt posterior fate.

slide23

The EGFR signal establishes

the A/P and D/V axial pattern

Red-actin

Green-gurken protein

As well as mRNA

The expression of EGFR pathway

target gene

specifying the anterior posterior axis of the drosophila embryo during oogenesis
Specifying the Anterior-Posterior Axis of the Drosophila Embryo During Oogenesis

http://www.youtube.com/watch?v=GntFBUa6nvs

specifying the anterior posterior axis of the drosophila embryo during oogenesis1
Specifying the Anterior-Posterior Axis of the Drosophila Embryo During Oogenesis

Protein kinase A

orients the microtubules

slide27

mRNA localization in the oocyte

Dynein-gurken and bicoid to the plus end

Kinesin—oskar to the minus end

slide28

The EGFR signal establishes

the A/P and D/V axial pattern

Gurken—TGFa

Torpedo--- EGFR

slide29

The localization of Gurken RNA

Cornichon, and Brainiac-

Modification and Transportation of the protein

K10, Squid localize gurken mRNA (3’UTR&

coding region)

Cappuccino and Spire –

cytoskeleton of

the oocyte

MAPK pathway

slide30

The Key determinant in D/V polarity is

pipe mRNA in follicle cells

slide31

The activation of Toll

windbeutel—ER protein

pipe—heparansulfate 2-o-sulfotransferase (Golgi)

nudel—serine protease

slide32

The dorsal-ventral pathway

Perivitelline space

Fig. 31-16

slide34

Toll pathway

Maternal genes—

Fertilization to cellular blastoderm

Dorsal system—for ventral structure

(mesoderm, neurogenic ectoderm)

Toll gene product rescue the defect

Toll mutant – dorsalized

(no ventral structure)

2. Transfer wt cytoplasm into

Toll mutant

specify a new dorsal-ventral axis

(injection site =ventral side)

spatzle (ligand) fragment diffuses

throughout the space

slide35

The mechanism of localization of

dorsal protein to the nucleus

Without Toll activation

Dorsal + cactus

Toll activation –

tube (adaptor) and pelle (kinase)

Phosphorylate cactus and promote

its degradation

B cell gene expression

Dorsal=NF-kB

Cactus=I-kB

slide39

Dorsal nuclear gradient

Activates—twist, snail (ventral)

Represses—dpp, zen (dorsal)

Fig. 31-19

toll protein activation results in a gradient of intranuclear dorsal protein
Toll protein activation results in a gradient of intranuclear dorsal protein

Fig. 5-8

Spatzle is processed in the perivitelline space after fertilization

slide41

Model for the subdivision of the dorso-ventral axis

into different regions by the gradient

in nuclear dorsal protein

Zygotic genes pattern the early embryo

Dorsal protein activates twist and snail

represses dpp, zen, tolloid

Rhomboid----neuroectoderm

Repressed by snail (not most ventral)

Binding sites for dorsal protein

in their regulatory regions

Fig. 5-13

slide42

Nuclear gradient in dorsal protein

Fig. 5-14

Dorsalized embryo—

Dorsal protein is not in nuclei

Dpp is everywhere

Twist and snail are not expressed

Threshold effect—integrating

Function of regulatory

binding sites

Regulatory element

=developmental switches

High affinity

(more dorsal region-low conc.)

Low affinity

(ventral side-high conc.)

dpp protein gradient
Dpp protein gradient

Cellularization---signal through transmembrane proteins

Dpp=BMP-4(TGF-b)

Dpp protein levels high, increase dorsal cells

short of gastrulation (sog) prevent the dpp spreading into neuroectoderm

Sog is degraded by Tolloid (most dorsal)

slide44

Snail—(mesoderm)

Reduce E-cadherin

cell migration

slide45

Microarray analysis

for gene expression

profile

slide46

The TGK-b/BMP signaling pathway

  • Antagonist
  • Proteases

dpp: decapentaplegic

Smad= Sma + Mad

Sma-C. elegans

Mad-Fly

Fig. 31-24

slide47

The Wnt and BMP pathways

are used in early development

Fig. 31-23

slide50

The Smad-dependent pathway activated by TGF-b

Type I, II receptor-Ser/Thr phosphorylation

slide51

The Smad-dependent pathway activated by TGF-b

Colorectal cancer: type II receptor

Pancreatic cancers: 50% Smad

One component between receptor

and gene regulation

slide52

De-repression of target genes in Dpp signaling

Activation

repression

groucho

Nature reviews genetics-8-663-2007

structural and functional domains of smad family
Structural and Functional Domains of Smad Family

TGFb , Activin: R-Smad 2,3

BMPs: R-Smad 1, 5, 8

Common Smad4-nucleocytoplasmic shuttling, DNA binding

Inhibitory Smads: I-Smad 6, 7

bioscience.org

integration of two signal pathways at the promoter
Integration of two signal pathways at the promoter

Smad2 and FAST

Smad3 and c-Jun/cFos

Cell,95,737, 1998

SBE: Smad binding element

ARE: activin-response element

TRE: TPA-response element (AP-1 binding)

XBE: transcription X

overview of tgf b family signaling
Overview of TGF-b family signaling

Development, 136-3691-2009

post translational modification of tgf b receptor
Post-translational modification of TGF-b receptor

Trends in Cell Biology, 19, 385-2009

the functions of the tgf b receptors are regulated by protein associations
The functions of the TGF-b receptors are regulated by protein associations

Trends in Cell Biology, 19, 385-2009

slide58

Different internalization pathways

resulted in distinct cellular effects

Trends in Cell Biology, 19, 385-2009