title: In vivo loss of function study reveals the short stature homeobox-containing (shox) gene plays indispensable roles in early embryonic growth and bone formation in zebrafish.
abstract: BACKGROUND
  Congenital loss of the SHOX gene is considered to be a genetic cause of short stature phenotype in Turner syndrome and Leri-Weill dyschondrosteosis patients. Though SHOX expression initiates during early fetal development, little is known about the embryonic roles of SHOX. The evolutionary conservation of the zebrafish shox gene and the convenience of the early developmental stages for analyses make zebrafish a preferred model. Here, we characterized structure, expression, and developmental roles of zebrafish shox through a loss-of-function approach.
  
  
  RESULTS
  We found a previously undiscovered Shox protein that has both a homeodomain and an OAR-domain in zebrafish. The shox transcript emerged during the segmentation period and it increased in later stages. The predominant domains of shox expression were mandibular arch, pectoral fin, anterior notochord, rhombencephalon, and mesencephalon, suggesting that Shox is involved in bone and neural development. Translational blockade of Shox mRNA by an antisense morpholino oligo delayed embryonic growth, which was restored by the co-overexpression of morpholino-resistant Shox mRNA. At later stages, impaired Shox expression markedly delayed the calcification process in the anterior vertebral column and craniofacial bones.
  
  
  CONCLUSIONS
  Our data demonstrate evolutionarily conserved Shox plays roles in early embryonic growth and in later bone formation.
authors.affiliation: Juntendo University Graduate School of Medicine, Tokyo, Japan; Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Sawada
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kamei
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hakuno
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology*; D005147:Facial Bones / Q000166:cytology / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D013131:Spine / Q000166:cytology / Q000196:embryology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D029961:Zebrafish Proteins
keywords: Danio rerio; Shox; body growth; cartilaginous ossification; morpholino-based knockdown