title: A novel Foxn1eGFP/+mouse model identifies Bmp4-induced maintenance of Foxn1 expression and thymic epithelial progenitor populations.
abstract: Although forkhead-box n1 (Foxn1) is a critical thymic epithelial cell regulator in thymus organogenesis, its association with epithelial differentiation and homeostasis in the postnatal and aged thymic microenvironment remains conflicting. Consequently, we have generated a Foxn1eGFP/+knock-in mouse model that allows for refined investigation of the aging thymic epithelium. This reporter line differs from those previously published in that concomitant expression of enhanced green fluorescent protein enables live cell sorting of Foxn1+cell populations. Our heterozygotes did not exhibit haploinsufficiency, with Foxn1 expression resembling that of wild-type mice. Comparative analysis between Foxn1 and enhanced green fluorescent protein at both the transcriptional and translational levels revealed co-localization, with progressive down-regulation observed predominantly in the aging cortical epithelium. Supplementation with bone morphogenetic protein (Bmp)-4 enhanced Foxn1 expression and colony forming efficiency in both embryonic and adult progenitor 3D cultures. Strikingly, selective maintenance of immature cortical and medullary epithelial cells was observed which is consistent with the higher Bmp receptor 2 expression levels seen in these progenitor populations. This study demonstrates the significance of our mouse model in unraveling the role of this master regulator in thymus development, homeostasis and aging, providing a faithful reporter system for phenotypic and functional investigations.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Marco
authors.initials: M
authors.lastname: Barsanti
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Joanna M C
authors.initials: JM
authors.lastname: Lim
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hun
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Lister
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Kahlia
authors.initials: K
authors.lastname: Wong
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Maree V
authors.initials: MV
authors.lastname: Hammett
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Ailin
authors.initials: A
authors.lastname: Lepletier
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boyd
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Giudice
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Ann P
authors.initials: AP
authors.lastname: Chidgey
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics; D006706:Homeostasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D013234:Stem Cells / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D051858:Forkhead Transcription Factors; C090140:Whn protein; D049452:Green Fluorescent Proteins; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: Aging; Bmp4; Foxn1; Foxn1eGFP mouse model; Thymic epithelial cell; Thymic epithelial progenitor cell; Thymus development