PI3K and Erk MAPK mediate ErbB signaling in Xenopus gastrulation.
ErbB signaling regulates cell adhesion and movements during Xenopus gastrulation, but the downstream pathways involved have not been elucidated. In this study, we show that phosphatidylinositol-3 kinase (PI3K) and Erk mitogen-activated protein kinase (MAPK) mediate ErbB signaling to regulate gastrulation. Both PI3K and MAPK function sequentially in mesoderm specification and movements, and ErbB signaling is important only for the late phase activation of these pathways to control cell behaviors. Activation of either PI3K or Erk MAPK rescues gastrulation defects in ErbB4 morphant embryos, and restores convergent extension in the trunk mesoderm as well as coherent cell migration in the head mesoderm. The two signals preferentially regulate different aspects of cell behaviors, with PI3K more efficient in rescuing cell adhesion and spreading and MAPK more effective in stimulating the formation of filopodia. PI3K and MAPK also weakly activate each other, and together they modulate gastrulation movements. Our results reveal that PI3K and Erk MAPK, which have previously been considered as mesodermal inducing signals, also act downstream of ErbB signaling to participate in regulation of gastrulation morphogenesis.
Nie
Shuyi
S
Department of Cell Biology, University of Alabama at Birmingham, 1530 3rd Avenue S., Birmingham, AL 35294, USA.
Chang
Chenbei
C
D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005775:Gastrula / Q000201:enzymology*; D054262:Gastrulation / Q000502:physiology*; D008648:Mesoderm / Q000201:enzymology; D018739:Oncogene Proteins v-erbB / Q000378:metabolism* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology
D018739:Oncogene Proteins v-erbB; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
Clin Cancer Res. 1999 Aug;5(8):2251-60
10473113
Mol Cell Neurosci. 2004 Dec;27(4):379-93
15555917
FASEB J. 2005 Jan;19(1):115-7
15629897
Exp Cell Res. 2005 Mar 10;304(1):305-16
15707595
EMBO Rep. 2005 May;6(5):426-31
15815683
Dev Biol. 2006 Sep 1;297(1):274-83
16919259
Dev Biol. 2007 Mar 1;303(1):93-107
17134691
J Biol Chem. 2007 Mar 23;282(12):8695-703
17242406
Biochim Biophys Acta. 2007 Aug;1773(8):1213-26
17112607
Dev Biol. 1997 Mar 1;183(1):9-20
9119118
J Cell Biol. 2000 Jan 24;148(2):385-97
10648571
Science. 2000 Feb 11;287(5455):1037-40
10669415
J Neurochem. 2000 Mar;74(3):979-87
10693928
Development. 2000 May;127(10):2227-38
10769246
Nature. 2000 May 4;405(6782):81-5
10811222
EMBO J. 2000 Jul 3;19(13):3159-67
10880430
Dev Biol. 2000 Dec 1;228(1):41-56
11087625
Development. 2001 Jan;128(1):35-44
11092809
Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37
11252954
J Cell Sci. 2001 Apr;114(Pt 8):1439-45
11282020
Genes Dev. 2001 May 1;15(9):1152-66
11331610
Differentiation. 2001 Dec;69(1):38-48
11776393
Cell. 2001 Dec 28;107(7):843-54
11779461
Development. 2002 Jan;129(1):37-52
11782399
EMBO Rep. 2002 Jan;3(1):69-75
11751577
Dev Biol. 2002 Apr 15;244(2):342-57
11944942
Cell. 2002 May 31;109(5):611-23
12062104
Dev Cell. 2002 Jun;2(6):695-706
12062082
FASEB J. 2002 Nov;16(13):1823-5
12354693
Genes Dev. 2003 Jan 15;17(2):295-309
12533515
Exp Cell Res. 2003 Mar 10;284(1):66-77
12648466
Exp Cell Res. 2003 Mar 10;284(1):99-110
12648469
Differentiation. 2003 Apr;71(3):171-205
12694202
Cancer Res. 2003 May 1;63(9):2172-8
12727836
Dev Biol. 2003 May 15;257(2):302-14
12729560
Genes Dev. 2003 Jul 1;17(13):1663-76
12842914
Dev Biol. 2003 Jul 15;259(2):318-35
12871704
Curr Biol. 2003 Aug 5;13(15):1279-89
12906787
Development. 2004 Jun;131(11):2727-36
15128658
Development. 2004 Jun;131(12):2769-79
15142973
J Cell Sci. 2004 Sep 15;117(Pt 20):4619-28
15371522
Oncogene. 2004 Oct 18;23(48):7928-46
15489911
Oncogene. 2004 Oct 18;23(48):7957-68
15489913
Cell. 1991 Jul 26;66(2):257-70
1649700
Methods Cell Biol. 1991;36:61-113
1811154
J Biol Chem. 1993 May 5;268(13):9803-10
8387505
Curr Opin Genet Dev. 1994 Feb;4(1):25-30
8193536
EMBO J. 1995 Jun 1;14(11):2491-8
7781601
Development. 1995 May;121(5):1475-86
7789277
Nature. 1995 Jul 6;376(6535):58-62
7541116
Development. 1995 Sep;121(9):3099-110
7555734
Mol Cell Biol. 1995 Dec;15(12):6686-93
8524233
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9641-4
8790383
Dev Biol. 1996 Aug 1;177(2):413-26
8806820
Curr Biol. 1996 Nov 1;6(11):1445-55
8939609
Development. 1997 Feb;124(4):827-37
9043064
Science. 1998 Jan 23;279(5350):558-60
9438848
Cell. 1998 Jul 10;94(1):109-18
9674432
Brain Res Mol Brain Res. 1998 Jul 15;58(1-2):59-73
9685585
J Biol Chem. 1998 Oct 23;273(43):28238-46
9774445
Dev Cell. 2005 May;8(5):689-701
15866160
J Cell Sci. 2005 Jun 15;118(Pt 12):2695-706
15944397
Development. 2005 Oct;132(20):4599-610
16176947
Dev Dyn. 2006 Feb;235(2):301-14
16258939
Bull Cancer. 2006 May;93(5):E44-52
16777617
Development. 1999 Jan;126(1):119-25
9834191
Oncogene. 1999 Apr 22;18(16):2607-15
10353604
Mol Cell Neurosci. 1999 Jun;13(6):415-29
10383827
Dev Biol. 1999 Sep 1;213(1):85-100
10452848