title: Runx1/AML1 hematopoietic transcription factor contributes to skeletal development in vivo.
abstract: The requirement of Runx2 (Cbfal/AML3), a runt homology domain transcription factor essential for bone formation and osteoblast differentiation, is well established. Although Runx2 is expressed in the developing embryo prior to ossification, yet in the absence of Runx2 initial formation of the skeleton is normal, suggesting a potential redundancy in function of Runx family members. Here we addressed expression of the hematopoietic family member Runx1 (AML1/Cbfa2) in relation to skeletal development using a LacZ knock-in mouse model (Runx1(lz/+)). The resulting fusion protein reflects Runx1 promoter activity in its native context. Our studies show that Runx1 is expressed by prechondrocytic tissue forming the cartilaginous anlagen in the embryo, resting zone chondrocytes, suture lines of the calvarium, and in periosteal and perichondral membranes of all bone. Runx1 continues to be expressed in these tissues in adult mice, but is absent in mature cartilage or mineralized bone. However, hyaline cartilage outside the bone environment (trachea, xiphoid tissues), and epithelium of many soft tissues (trachea, thyroid, lung, skin) also express Runx1. The robust expression of Runx1 in vivo in chondroblasts at sites of cartilage growth and in osteoblasts at sites of new bone formation, suggests that Runx1 expression may be related to osteochondroprogenitor cell differentiation. This observation is further supported by high expression of Runx1 in ex vivo cultures of marrow stromal cells and calvarial derived osteoblasts from Runx1(lz/+) mice. These data indicate that Runx1 may contribute to the early stages of skeletogenesis and continues to function in the progenitor cells of tissues that support bone formation in the adult.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0106, USA. jane.lian@umassmed.edu
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Eva
authors.initials: E
authors.lastname: Balint
authors.forename: Amjad
authors.initials: A
authors.lastname: Javed
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
authors.forename: Regan
authors.initials: R
authors.lastname: Vitti
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Quinlan
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Andre J
authors.initials: AJ
authors.lastname: Van Wijnen
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Nancy
authors.initials: N
authors.lastname: Speck
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D011518:Proto-Oncogene Proteins; D012863:Skeleton; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors