slide1
Download
Skip this Video
Download Presentation
Drosophila

Loading in 2 Seconds...

play fullscreen
1 / 27

Drosophila - PowerPoint PPT Presentation


  • 156 Views
  • Uploaded on

variation. Drosophila. Egg chamber. Eggshell (chorion). ?. ?. Y*. The experimental system. Cellular responses. EGFR/ErbB Signaling Network. Invertebrates. Vertebrates. ErbB3. EGFR. ErbB2. EGFR. signal diversification • inhibitors ?. signal diversification: • heterodimerization.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Drosophila' - fadhila


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

variation

Drosophila

Egg chamber

Eggshell (chorion)

?

?

Y*

The experimental system

Cellular responses

slide2

EGFR/ErbB Signaling Network

Invertebrates

Vertebrates

ErbB3

EGFR

ErbB2

EGFR

signal diversification

• inhibitors ?

signal diversification:

• heterodimerization

slide3

The EGFR network and dorsal patterning

Amplification

Spitz

Vein

Inhibition

Argos

Site of

Appendage

Formation

chorion

Profile of

EGFR activity: WT

Initiation

Gurken

slide4

Molecular

Genetic

Phylogenetic

identify

targets

Create differences

= mutant screens

Identify differences

= other species

How can we identify components of the EGFR network?

slide5

ligand

Kek1

Kek1 and feedback regulation of EGFR

EGFR

kek1 expression

?

No overt phenotype ?

slide7

WT

kek1-

WT

egfr-

egfr-; kek1-

BR-C

rho

aos

Evidence that endogenous kek1 inhibits EGFR signaling

slide8

Profile of

EGFR activity: WT

Profile of

EGFR activity: kek1-

What role does Kek1 have in dorsal patterning?

Initiation

Gurken

Amplification

Spitz

Vein

Inhibition

Argos

Site of

Appendage

Formation

slide9

Kek1 inhibits EGFR signaling

1. Mechanism

2. Sequence requirements

ligand

EGFR

Kek1

EGFR

slide10

Kek1

Kek1

Y*

No signaling - ventralized

Signaling - dorsalized

Kek1 inhibits EGFR signaling

1. Mechanism

Ligand sink vs heterodimer

EGFR

slide11

Kek1

EGFR

Kek1 inhibits EGFR signaling

2. Sequence requirements ?

Domain swaps

slide12

Kek1 inhibits EGFR signaling

2. Sequence requirements ?

The Kek1 LRRs are sufficient

for binding EGFR…

…but insufficient for full inhibition in vivo!

L

LIT

slide13

[GMR-GAL4*] [UAS-kek1*gfp]

[GMR-GAL4] [UAS-kek1gfp]

____________________

+

____________________

CyO

w; iso2; iso3

EMS

EMS

Identifying residues important for Kek1/EGFR interaction

P

suppressor

F1

slide14

Suppressors of Kek1

= egfr alleles

Identifying residues important for Kek1/EGFR interaction

Knockouts of Kek1

slide15

Kek1 = a novel inhibitory component of the EGFR network

Binding

&

Inhibition

Kek1

EGFR

Trafficking

&

Stability

slide16

X

Mutations in

vital gene =

lethality

Identification of EGFR components

Genetic approach

Directed mosaics

Drosophila

Egg chamber

dCBP

bwk

WT

slide17

wild type

EGFR

dCBP

pnt

dCBP mediates feedback inhibition of EGFR signaling

slide18

dCBP -

dCBP mediates feedback inhibition of EGFR signaling

wt

Initiation

Gurken

Amplification

Spitz

Vein

Inhibition

Argos

Site of

Appendage

Formation

chorion

slide19

amplification

inhibition

attenuation

Rhomboid

Kek1

dCBP/Pointed

Bwk

Argos

Egfr mediated epithelial patterning

Gurken

EGFR

Egfr transcriptional

targets

slide20

Identification of EGFR components

1

4

2

2

3

2

4

L.Throckmorton, 1950

Phylogenetic approach

4

latifasciaformis

slide21

EGFR signaling and appendage patterning

What components of the pathway underlie

variation in dorsal appendage patterning?

Intraspecific

analysis

Interspecific

analysis

map natural variation

Characterize patterning

at molecular level

dose-dependent screen

? genes

slide22

Interspecific analysis: Kek1

A

F

G

B

C

H

D

I

J

E

D. melanogaster

D. virilis

slide23

grkHK36 egfrCO

+ +

Intraspecific analysis

• Does quantitative variation in the EGFR network exist?

• If so, what molecular components underlie this variation?

- template for interspecific variation?

Appendage variation

WT/V0 V1a V1b V2 V3 V4

slide25

3

EGFR signaling and appendage patterning

Identifying novel

dose-dependent

EGFR components

grkHK36 egfrCO

+ +

slide26

amplification

inhibition

attenuation

Rhomboid

Kek1

dCBP/Pointed

Bwk

Argos

Egfr mediated epithelial patterning

Gurken

EGFR

Egfr transcriptional

targets

slide27

Acknowledgements

Andrea Cowden

Omar Hasnie

Matt Rubin

Kyle Payne

Diego Alvarado

Alex Doetsch

Tim Evans

Christina MacLaren

Amy Rice

Anne Scherer

Fred Derheimer

Libbie Eakin

Paul Miller

Christopher Skipwith

Brandon Weasner

ad