Nanog-like regulates endoderm formation through the Mxtx2-Nodal pathway.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Xu, C; Fan, ZP; Müller, P; Fogley, R; DiBiase, A; Trompouki, E; Unternaehrer, J; Xiong, F; Torregroza, I; Evans, T; Megason, SG; Daley, GQ; Schier, AF; Young, RA; Zon, LI

Published Date

  • March 2012

Published In

Volume / Issue

  • 22 / 3

Start / End Page

  • 625 - 638

PubMed ID

  • 22421047

Pubmed Central ID

  • PMC3319042

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

International Standard Serial Number (ISSN)

  • 1534-5807

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2012.01.003

Language

  • eng