PUBLICATION

Nanog-like Regulates Endoderm Formation through the Mxtx2-Nodal Pathway

Authors
Xu, C., Fan, Z.P., Müller, P., Fogley, R., Dibiase, A., Trompouki, E., Unternaehrer, J., Xiong, F., Torregroza, I., Evans, T., Megason, S.G., Daley, G.Q., Schier, A.F., Young, R.A., and Zon, L.I.
ID
ZDB-PUB-120326-3
Date
2012
Source
Developmental Cell   22(3): 625-238 (Journal)
Registered Authors
Evans, Todd, Megason, Sean, Schier, Alexander, Zon, Leonard I.
Keywords
none
Datasets
GEO:GSE34683, GEO:GSE34684, GEO:GSE34682
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Embryo, Nonmammalian/metabolism
  • Endoderm/metabolism*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Molecular Sequence Data
  • Nodal Signaling Ligands/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
22421047 Full text @ Dev. Cell
Abstract

In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog, but the in vivo analysis of Nanog has been hampered by its requirement for early mouse development. In an effort to examine the role of Nanog in vivo, we identified a zebrafish Nanog ortholog and found that its knockdown impaired endoderm formation. Genome-wide transcription analysis revealed that nanog-like morphants fail to develop the extraembryonic yolk syncytial layer (YSL), which produces Nodal, required for endoderm induction. We examined the genes that were regulated by Nanog-like and identified the homeobox gene mxtx2, which is both necessary and sufficient for YSL induction. Chromatin immunoprecipitation assays and genetic studies indicated that Nanog-like directly activates mxtx2, which, in turn, specifies the YSL lineage by directly activating YSL genes. Our study identifies a Nanog-like-Mxtx2-Nodal pathway and establishes a role for Nanog-like in regulating the formation of the extraembryonic tissue required for endoderm induction.

Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping