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Although previous studies have identified several key transcription factors in the generation process of the vertebrate nervous system, the intracellular signalling pathways that function in this process have remained unclear. Here we identify the evolutionarily conserved mitogen-activated protein kinase kinase 5 (MEK5)-extracellular signal-regulated kinase 5 (ERK5) pathway as an essential regulator in neural differentiation. Knockdown of Xenopus ERK5 or Xenopus MEK5 with antisense morpholino oligonucleotides results in the reduced head structure and inhibition of neural differentiation. Moreover, forced activation of the MEK5-ERK5 module on its own induces neural differentiation. In addition, we show that the MEK5-ERK5 pathway is necessary for the neuralizing activity of SoxD, a regulator of neural differentiation, and is sufficient for the expression of Xngnr1, a proneural gene. These results show that the MEK5-ERK5 pathway has an essential role in the regulation of neural differentiation downstream of SoxD and upstream of Xngnr1.
Abe,
Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase.
1996, Pubmed
Abe,
Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase.
1996,
Pubmed
Davis,
Signal transduction by the JNK group of MAP kinases.
2000,
Pubmed
De Robertis,
Dorsal-ventral patterning and neural induction in Xenopus embryos.
2004,
Pubmed
,
Xenbase
Fainsod,
The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4.
1997,
Pubmed
,
Xenbase
Greene,
Identification and characterization of a novel member of the fibroblast growth factor family.
1998,
Pubmed
Hayashi,
Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure.
2004,
Pubmed
Hemmati-Brivanlou,
Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity.
1994,
Pubmed
,
Xenbase
Hikasa,
A Xenopus homolog of a human p53-activated gene, PA26, is specifically expressed in the notochord.
2001,
Pubmed
,
Xenbase
Kamakura,
Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus.
1999,
Pubmed
Kato,
BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C.
1997,
Pubmed
Kato,
Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor.
1998,
Pubmed
Kengaku,
bFGF as a possible morphogen for the anteroposterior axis of the central nervous system in Xenopus.
1995,
Pubmed
,
Xenbase
Kesavan,
MEKK2 regulates the coordinate activation of ERK5 and JNK in response to FGF-2 in fibroblasts.
2004,
Pubmed
Kusakabe,
Xenopus FRS2 is involved in early embryogenesis in cooperation with the Src family kinase Laloo.
2001,
Pubmed
,
Xenbase
Kyriakis,
Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation.
2001,
Pubmed
Lamb,
Neural induction by the secreted polypeptide noggin.
1993,
Pubmed
,
Xenbase
Launay,
A truncated FGF receptor blocks neural induction by endogenous Xenopus inducers.
1996,
Pubmed
,
Xenbase
Liu,
ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons.
2003,
Pubmed
Ma,
Identification of neurogenin, a vertebrate neuronal determination gene.
1996,
Pubmed
,
Xenbase
Mizuseki,
SoxD: an essential mediator of induction of anterior neural tissues in Xenopus embryos.
1998,
Pubmed
,
Xenbase
Molkentin,
Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C.
1996,
Pubmed
Munoz-Sanjuan,
Expression of chicken fibroblast growth factor homologous factor (FHF)-1 and of differentially spliced isoforms of FHF-2 during development and involvement of FHF-2 in chicken limb development.
1999,
Pubmed
Muñoz-Sanjuán,
Neural induction, the default model and embryonic stem cells.
2002,
Pubmed
Nishida,
The MAP kinase cascade is essential for diverse signal transduction pathways.
1993,
Pubmed
,
Xenbase
Nitta,
XSIP1 is essential for early neural gene expression and neural differentiation by suppression of BMP signaling.
2004,
Pubmed
,
Xenbase
Pera,
Neural and head induction by insulin-like growth factor signals.
2001,
Pubmed
,
Xenbase
Pera,
Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction.
2003,
Pubmed
,
Xenbase
Piccolo,
Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4.
1996,
Pubmed
,
Xenbase
Regan,
Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defects.
2002,
Pubmed
Richard-Parpaillon,
The IGF pathway regulates head formation by inhibiting Wnt signaling in Xenopus.
2002,
Pubmed
,
Xenbase
Robinson,
Mitogen-activated protein kinase pathways.
1997,
Pubmed
Sasai,
Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus.
1995,
Pubmed
,
Xenbase
Sasai,
Identifying the missing links: genes that connect neural induction and primary neurogenesis in vertebrate embryos.
1998,
Pubmed
Sohn,
ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive repressor of vascular endothelial growth factor expression.
2002,
Pubmed
Sturgill,
Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6.
1991,
Pubmed
Wang,
Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway.
2005,
Pubmed
Yan,
Knockout of ERK5 causes multiple defects in placental and embryonic development.
2003,
Pubmed
