title: Roles of GASP-1 and GDF-11 in Dental and Craniofacial Development.
abstract: OBJECTIVE
  Growth and differentiation factor-11 (GDF-11) is a TGF-β family member that plays important regulatory roles in development of multiple tissues which include axial skeletal patterning, palatal closure, and tooth formation. Proteins that have been identified as GDF-11 inhibitors include GDF-associated serum protein-1 (GASP-1) and GASP-2. Recently, we found that mice genetically engineered to lack bothGasp1andGdf11have an increased frequency of cleft palate. The goal of this study was to investigate the roles of GDF-11 and its inhibitors, GASP-1 and GASP-2, during dental and craniofacial development and growth.
  
  
  METHODS
  Mouse genetic studies were used in this study. Homozygous knockout mice forGasp1(Gasp1-/-) andGasp2(Gasp2-/-) were viable and fertile, butGdf11homozygous knockout (Gdf11-/-) mice died within 24 hours after birth. The effect of eitherGasp1orGasp2deletion inGdf11-/-mice during embryogenesis was evaluated inGasp1-/-;Gdf11-/-andGasp2-/-;Gdf11-/-mouse embryos at 18.5 days post-coitum (E18.5). For the analysis of adult tissues, we usedGasp1-/-;Gdf11+/-andGasp2-/-;Gdf11+/-mice to evaluate the potential haploinsufficiency ofGdf11inGasp1-/-andGasp2-/-mice.
  
  
  RESULTS
  AlthoughGasp2expression decreased after E10.5,Gasp1expression was readily detected in various ectodermal tissues at E17.5, including hair follicles, epithelium in nasal cavity, retina, and developing tooth buds. Interestingly,Gasp1-/-;Gdf11-/-mice had abnormal formation of lower incisors: tooth buds for lower incisors were under-developed or missing. AlthoughGdf11+/-mice were viable and had mild transformations of the axial skeleton, no specific defects in the craniofacial development have been observed inGdf11+/-mice. However, loss ofGasp1inGdf11+/-mice occasionally resulted in small and abnormally shaped auricles.
  
  
  CONCLUSIONS
  These findings suggest that both GASP-1 and GDF-11 play important roles in dental and craniofacial development both during embryogenesis and in adult tissues.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, PCTB 803, Baltimore, MD 21205, USA.
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, PCTB 803, Baltimore, MD 21205, USA.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Lee
keywords: Cleft palate; Craniofacial abnormalities; GASP-1; GDF-11; Microtia; Tooth abnormalities