title: Nanog-like regulates endoderm formation through the Mxtx2-Nodal pathway.
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.
authors.affiliation: Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Xu
authors.forename: Zi Peng
authors.initials: ZP
authors.lastname: Fan
authors.forename: Patrick
authors.initials: P
authors.lastname: Müller
authors.forename: Rachel
authors.initials: R
authors.lastname: Fogley
authors.forename: Anthony
authors.initials: A
authors.lastname: DiBiase
authors.forename: Eirini
authors.initials: E
authors.lastname: Trompouki
authors.forename: Juli
authors.initials: J
authors.lastname: Unternaehrer
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Xiong
authors.forename: Ingrid
authors.initials: I
authors.lastname: Torregroza
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
authors.forename: Sean G
authors.initials: SG
authors.lastname: Megason
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D000071317:Nanog Homeobox Protein; D055456:Nodal Signaling Ligands / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071317:Nanog Homeobox Protein; C572119:Nanog protein, zebrafish; D055456:Nodal Signaling Ligands; D029961:Zebrafish Proteins; C409450:mxtx2 protein, zebrafish; C485171:ndr1 protein, zebrafish; C512832:ndr2 protein, zebrafish