Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm.
BACKGROUND
We investigated the roles of p120 catenin, Cdc42, Rac1, and RhoA GTPases in regulating migration of presomitic mesoderm cells in zebrafish embryos. p120 catenin has dual roles: It binds the intracellular and juxtamembrane region of cadherins to stabilize cadherin-mediated adhesion with the aid of RhoA GTPase, and it activates Cdc42 GTPase and Rac1 GTPase in the cytosol to initiate cell motility.


RESULTS
During gastrulation of zebrafish embryos, knockdown of the synthesis of zygotic p120 catenin δ1 mRNAs with a splice-site morpholino caused lateral widening and anterior-posterior shortening of the presomitic mesoderm and somites and a shortened anterior-posterior axis. These phenotypes indicate a cell-migration effect. Co-injection of low amounts of wild-type Cdc42 or wild-type Rac1 or dominant-negative RhoA mRNAs, but not constitutively-active Cdc42 mRNA, rescued these p120 catenin δ1-depleted embryos.


CONCLUSIONS
These downstream small GTPases require appropriate spatiotemporal stimulation or cycling of GTP to guide mesodermal cell migration. A delicate balance of Rho GTPases and p120 catenin underlies normal development.
Department of Biology, University of Washington, Seattle, WA 98195, USA.
Cynthia L
CL
Hsu
Claire P
CP
Muerdter
Abhay D
AD
Knickerbocker
Ryan M
RM
Walsh
Martha A
MA
Zepeda-Rivera
Kevin H
KH
Depner
Maya
M
Sangesland
Trinidad B
TB
Cisneros
Ju Youn
JY
Kim
Patricia
P
Sanchez-Vazquez
Lidia
L
Cherezova
Rainy D
RD
Regan
Nadia M
NM
Bahrami
Elizabeth A
EA
Gray
Andrew Y
AY
Chan
Terry
T
Chen
Milly Y
MY
Rao
Merrill B
MB
Hille
D000818:Animals; D015153:Blotting, Western; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003001:Cloning, Molecular; D054262:Gastrulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006160:Guanosine Triphosphate / Q000378:metabolism; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D000095002:Delta Catenin
D051177:Catenins; D016376:Oligonucleotides, Antisense; D006160:Guanosine Triphosphate; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D000095002:Delta Catenin