title: The differentiation and movement of presomitic mesoderm progenitor cells are controlled by Mesogenin 1.
abstract: Somites are formed from the presomitic mesoderm (PSM) and give rise to the axial skeleton and skeletal muscles. The PSM is dynamic; somites are generated at the anterior end, while the posterior end is continually renewed with new cells entering from the tailbud progenitor region. Which genes control the conversion of tailbud progenitors into PSM and how is this process coordinated with cell movement? Using loss- and gain-of-function experiments and heat-shock transgenics we show in zebrafish that the transcription factor Mesogenin 1 (Msgn1), acting with Spadetail (Spt), has a central role. Msgn1 allows progression of the PSM differentiation program by switching off the progenitor maintenance genes ntl, wnt3a, wnt8 and fgf8 in the future PSM cells as they exit from the tailbud, and subsequently induces expression of PSM markers such as tbx24. msgn1 is itself positively regulated by Ntl/Wnt/Fgf, creating a negative-feedback loop that might be crucial to regulate homeostasis of the progenitor population until somitogenesis ends. Msgn1 drives not only the changes in gene expression in the nascent PSM cells but also the movements by which they stream out of the tailbud into the PSM. Loss of Msgn1 reduces the flux of cells out of the tailbud, producing smaller somites and an enlarged tailbud, and, by delaying exhaustion of the progenitor population, results in supernumerary tail somites. Through its combined effects on gene expression and cell movement, Msgn1 (with Spt) plays a key role both in genesis of the paraxial mesoderm and in maintenance of the progenitor population from which it derives.
authors.affiliation: Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal. ritafior@fm.ul.pt
authors.forename: Rita
authors.initials: R
authors.lastname: Fior
authors.forename: Adrienne A
authors.initials: AA
authors.lastname: Maxwell
authors.forename: Taylur P
authors.initials: TP
authors.lastname: Ma
authors.forename: Annalisa
authors.initials: A
authors.lastname: Vezzaro
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Amacher
authors.forename: Julian
authors.initials: J
authors.lastname: Lewis
authors.forename: Leonor
authors.initials: L
authors.lastname: Saúde
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D058948:Cell Tracking; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D019170:Somites / Q000196:embryology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013623:Tail / Q000196:embryology; D060726:Torso / Q000196:embryology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; C481359:msgn1 protein, zebrafish; C112539:tbx16 protein, zebrafish