title: Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures.
abstract: During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures.
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: ekague@ib.usp.br.
authors.forename: Erika
authors.initials: E
authors.lastname: Kague
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Roy
authors.affiliation: Department of Biology, University of Massachusetts, Amherst, MA, USA.
authors.forename: Garrett
authors.initials: G
authors.lastname: Asselin
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Gui
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Simonet
authors.affiliation: Cell and Molecular Biology Graduate Program, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stanley
authors.affiliation: Department of Biology, University of Massachusetts, Amherst, MA, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Albertson
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: shanfish@bu.edu.
authors.forename: Shannon
authors.initials: S
authors.lastname: Fisher
mesh_terms: D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002356:Cartilage / Q000196:embryology; D003393:Cranial Sutures / Q000196:embryology*; D006801:Humans; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics; D015398:Signal Transduction; D012886:Skull / Q000196:embryology; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D059467:Transcriptome; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors; D029961:Zebrafish Proteins; C541742:sp7 protein, zebrafish
keywords: Craniofacial skeleton; Osteogenesis; Osterix/Sp7; Sutures; Zebrafish mutant