Multiple Wnt Signaling Pathways Converge to Orient
This presentation is the property of its rightful owner.
Sponsored Links
1 / 17

Multiple Wnt Signaling Pathways Converge to Orient PowerPoint PPT Presentation


  • 60 Views
  • Uploaded on
  • Presentation posted in: General

Multiple Wnt Signaling Pathways Converge to Orient the Mitotic Spindle in Early C. elegans Embryos. Walston T. et al . Developmental Cell , Vol. 7, 831–841, December, 2004. ABpl. Background. The fate of the EMS daughters is controlled by a Wnt/b-cat pathway.

Download Presentation

Multiple Wnt Signaling Pathways Converge to Orient

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


Multiple Wnt Signaling Pathways Converge to Orient

the Mitotic Spindle in Early C. elegans Embryos

Walston T. et al.

Developmental Cell, Vol. 7, 831–841, December, 2004


ABpl

Background

  • The fate of the EMS daughters is controlled

  • by a Wnt/b-cat pathway.

  • The orientation of the EMS division is

    controlled by a different Wnt pathway involving

    Wnt(MOM-2), Porcupine(Porc;MOM-1),

    Fz(MOM-5), GSK-3(GSK-3b) and CK1a(KIN-19).

  • A pathway involving MES-1, a receptor tyrosine

    kinase, and SRC-1, a Src family tyrosine kinase,

    acts redundantly with Wnt signaling with respect

    to the fate of EMS daughters and the orientation

    of the EMS spindle.

  • mom-1 (Porc), mom-2 (Wnt), mom-5 (Fz), and

    mom-3 (uncloned), cause spindle alignment

    defects in the ABar blastomere of the 8-cell

    embryo.


Background


We demonstarate...

  • Although many Wnt signaling components have been identified that participate in spindle orientation, the role of the Dsh family has not been clearly characterized.

  • (dsh-1, dsh-2, mig-5)

  • Loss of function of the CKIhomolog, kin-19, causes defects in the fate of EMS daughter cells. Although the role of CKI in spindle alignment has not been examined, CKIlocalizes to centrosomes and mitotic spindles in vertebrate systems.

  • The nontranscriptional Wnt spindle alignment pathway requires contact from the C blastomereto align the spindle of ABar.

  • Wnt/b-catenin pathway regulates the timing of spindle rotation in ABar,presumably by specifying the fate of neighboring blastomeres.


Defects in Alignment of the EMS and ABar Spindles.

dsh-2(or302)

dsh-1(RNAi); dsh-2(or302); mig-5(RNAi)


Defects in EMS


KIN-19/CKⅠ localizes to centrosomes and DSH-2 accumulates between P2 and EMS.

condensed

chromosome

microtubule

Consistent with P2 signaling to EMS to specify

endoderm fate and EMS spindle orientation.

KIN-19 RNAi → does not affect Dsh-2 localization.


Fz

APC

Axin

b-cat

NEMO

TCF

RNA pol.

Spindle defects in ABar.

Positive : Dsh, CKⅠ, GSK-3, Src (Dsh background)

Negative : JNK, APC, Axin, b-cat, NEMO, TCF, RNA pol.


C

Mom-2(Wnt)

Mom-5(Fz)

Mom-5(Fz)

canonical

non-canonical

ABar

EMS

Contact with the C blastomere aligns the spindle in ABar.

Caudal

homolog

laser

killed


dsh-2(RNAi); mig-5(RNAi)

wrm-1(RNAi)

ABar spindle defects visualized by b-tubulin::GFP

TBB-2/ b-tubulin::GFP


Three Wnt signaling pathways operate in the Early C. elegans embryos.


Discussion

Gbg signaling in spindle orientation ??

GSK-3 in spindle orientation ??


Heterotrimeric G-protein in spindle orientation

D

ABp

ABa

P2

P

A

EMS

V

Gb : GPB-1, GPB-2

Gg : GPC-1, GPC-2

Gotta M et al, Nat Cell Biol, 2001.


Heterotrimeric G-protein in spindle orientation

C. elegans has 20Ga genes.

→ GOA-1, GPA-16

Conclusion : Gbg signaling, not Ga, participates spindle orientation in C. elegans.

Gotta M et al, Nat Cell Biol, 2001.


Cdc42 regulates GSK-3b and APC to control cell polarity.

Astrocyte

MTOC : microtubule organizing centre

There is a larger complex containing GSK-3b, Par6, PKCz.

Scratch-induced cell migration assay

: Cdc42, p-GSK-3b, b-cat and APC localize at the leading edge of migrating cell.

Etienne-Manneville S et al. Nature, 2003.


Activation of Gbg signaling downstream of Wnt-11/Xfz7 regulates Cdc42 activity.

During xenopus gastrulation

Penzo-Mendez A et al. Dev Biol, 2003.


Canonical Wnt

Non-canonical Wnt

Leading edge

Cdc42, p-GSK-3b

b-cat, APC

Fz

Fz

Mes-1

Gbg

Dvl

Dvl

PKC

Src

Cdc42

RhoA

Par-6

Dvl-1 ?

Dvl-2 ?

Dvl-3 ?

PKCz

GSK-3b

CKⅠ

MEKK, SEK

Axin

APC

b-cat

JNK

Polarity

b-cat

b-cat

b-cat

b-cat

Cell fate,

spindle rotation

Tcf/Lef


  • Login