title: Meteorin regulates mesendoderm development by enhancing nodal expression.
abstract: During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.
authors.affiliation: School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea ; Division of Molecular and Life Science, Department of Life Sciences, POSTECH, Pohang, South Korea.
authors.forename: Yoon-Young
authors.initials: YY
authors.lastname: Kim
authors.affiliation: Division of Molecular and Life Science, Department of Life Sciences, POSTECH, Pohang, South Korea.
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Moon
authors.affiliation: Division of Molecular and Life Science, Department of Life Sciences, POSTECH, Pohang, South Korea.
authors.forename: Min-chul
authors.initials: MC
authors.lastname: Kwon
authors.affiliation: School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea ; Division of Molecular and Life Science, Department of Life Sciences, POSTECH, Pohang, South Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Shin
authors.affiliation: School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea ; Division of Molecular and Life Science, Department of Life Sciences, POSTECH, Pohang, South Korea.
authors.forename: Sun-Kyoung
authors.initials: SK
authors.lastname: Im
authors.affiliation: School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Hyun-A
authors.initials: HA
authors.lastname: Kim
authors.affiliation: Division of Molecular and Life Science, Department of Life Sciences, POSTECH, Pohang, South Korea.
authors.forename: Jin-Kwan
authors.initials: JK
authors.lastname: Han
authors.affiliation: School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Young-Yun
authors.initials: YY
authors.lastname: Kong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D058732:Embryoid Bodies / Q000166:cytology; D005260:Female; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055457:Nodal Protein / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D055457:Nodal Protein; C502098:meteorin protein, mouse