title: Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation.
abstract: Neuromesodermal (NM) stem cells generate neural and paraxial presomitic mesoderm (PSM) cells, which are the respective progenitors of the spinal cord and musculoskeleton of the trunk and tail. The Wnt-regulated basic helix-loop-helix (bHLH) transcription factor mesogenin 1 (Msgn1) has been implicated as a cooperative regulator working in concert with T-box genes to control PSM formation in zebrafish, although the mechanism is unknown. We show here that, in mice, Msgn1 alone controls PSM differentiation by directly activating the transcriptional programs that define PSM identity, epithelial-mesenchymal transition, motility and segmentation. Forced expression of Msgn1 in NM stem cells in vivo reduced the contribution of their progeny to the neural tube, and dramatically expanded the unsegmented mesenchymal PSM while blocking somitogenesis and notochord differentiation. Expression of Msgn1 was sufficient to partially rescue PSM differentiation in Wnt3a(-/-) embryos, demonstrating that Msgn1 functions downstream of Wnt3a as the master regulator of PSM differentiation. Our data provide new insights into how cell fate decisions are imposed by the expression of a single transcriptional regulator.
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Ravindra B
authors.initials: RB
authors.lastname: Chalamalasetty
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Garriock
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Dunty
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, MD 21702, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kennedy
authors.affiliation: CCRIFX Bioinformatics Core, Leidos Biomedical Research, FNLCR, Frederick, MD 21702, USA.
authors.forename: Parthav
authors.initials: P
authors.lastname: Jailwala
authors.affiliation: CCRIFX Bioinformatics Core, Leidos Biomedical Research, FNLCR, Frederick, MD 21702, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Si
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, MD 21702, USA yamagute@mail.nih.gov.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008156:Luciferases; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D018482:Muscle, Skeletal / Q000196:embryology*; D009420:Nervous System / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060509:Wnt3A Protein / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008156:Luciferases; D060509:Wnt3A Protein; C410883:Msgn1 protein, mouse; C555511:Wnt3a protein, mouse
keywords: Differentiation; EMT; Embryonic stem cell; Motility; Mouse; PSM; Paraxial mesoderm; Somite; Wnt; bHLH transcription factor