title: Twist controls skeletal development and dorsoventral patterning by regulating runx2 in zebrafish.
abstract: BACKGROUND
  Twist1a and twist1b are the principal components of twists that negatively regulate a number of cellular signaling events. Expression of runx2 and downstream targets is essential for skeletal development and ventral organizer formation and specification in early vertebrate embryos, but what controls ventral activity of maternal runx2 and how twists function in zebrafish embryogenesis still remain unclear.
  
  
  RESULTS
  By studying the loss of twist induced by injection of morpholino-oligonucleotide in zebrafish, we found that twist1a and twist1b, but not twist2 or twist3, were required for proper skeletal development and dorsoventral patterning in early embryos. Overexpression of twist1a or twist1b following mRNA injection resulted in deteriorated skeletal development and formation of typical dorsalized embryos, whereas knockdown of twist1a and twist1b led to the formation of abnormal embryos with enhanced skeletal formation and typical ventralized patterning. Overexpression of twist1a or twist1b decreased the expression of runx2b, whereas twist1a and twist1b knockdown increased runx2b expression. We have further demonstrated that phenotypes induced by twist1a and twist1b knockdown were rescued by runx2b knockdown.
  
  
  CONCLUSIONS
  Together, these results suggest that twist1a and twist1b control skeletal development and dorsoventral patterning by regulating runx2b in zebrafish and provide potential targets for the treatment of diseases or syndromes associated with decreased skeletal development.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Der-Chih
authors.initials: DC
authors.lastname: Yang
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Tsai
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Liao
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Fu
authors.forename: Huey-Jen
authors.initials: HJ
authors.lastname: Tsay
authors.forename: Tung-Fu
authors.initials: TF
authors.lastname: Huang
authors.forename: Yau-Hung
authors.initials: YH
authors.lastname: Chen
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics*; D001846:Bone Development / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C502545:Runx2a protein, zebrafish; C528432:twist1a protein, zebrafish
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