Nanog-like Regulates Endoderm Formation through the Mxtx2-Nodal Pathway
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Xu-2012-Nanog-like Regulates.pdf
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Author(s)
Xu, Cong
Fan, Zi Peng
Fogley, Rachel
DiBiase, Anthony
Trompouki, Eirini
Unternaehrer, Juli
Xiong, Fengzhu
Torregroza, Ingrid
Evans, Todd
Megason, Sean G.
Date Issued
March 2012
Journal
Developmental Cell
Publisher
Elsevier
Citation
Xu, Cong, Zi Peng Fan, Patrick Muller, Rachel Fogley, Anthony DiBiase, Eirini Trompouki, Juli Unternaehrer, et al. “Nanog-Like Regulates Endoderm Formation through the Mxtx2-Nodal Pathway.” Developmental Cell 22, no. 3 (March 2012): 625–638. © 2012 Elsevier Inc.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.devcel.2012.01.003
