title: Supt20 is required for development of the axial skeleton.
abstract: Somitogenesis and subsequent axial skeletal development is regulated by the interaction of pathways that determine the periodicity of somite formation, rostrocaudal somite polarity and segment identity. Here we use a hypomorphic mutant mouse line to demonstrate that Supt20 (Suppressor of Ty20) is required for development of the axial skeleton. Supt20 hypomorphs display fusions of the ribs and vertebrae at lower thoracic levels along with anterior homeotic transformation of L1 to T14. These defects are preceded by reduction of the rostral somite and posterior shifts in Hox gene expression. While cycling of Notch target genes in the posterior presomitic mesoderm (PSM) appeared normal, expression of Lfng was reduced. In the anterior PSM, Mesp2 expression levels and cycling were unaffected; yet, expression of downstream targets such as Lfng, Ripply2, Mesp1 and Dll3 in the prospective rostral somite was reduced accompanied by expansion of caudal somite markers such as EphrinB2 and Hes7. Supt20 interacts with the Gcn5-containing SAGA histone acetylation complex. Gcn5 hypomorphic mutant embryos show similar defects in axial skeletal development preceded by posterior shift of Hoxc8 and Hoxc9 gene expression. We demonstrate that Gcn5 and Supt20 hypomorphs show similar defects in rostral-caudal somite patterning potentially suggesting shared mechanisms.
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Sunita
authors.initials: S
authors.lastname: Warrier
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Samer
authors.initials: S
authors.lastname: Nuwayhid
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Sabatino
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA; Institute for Biomedical Sciences, The George Washington University, Washington, DC 20052, USA.
authors.forename: Kelsey F
authors.initials: KF
authors.lastname: Sugrue
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA. Electronic address: izohn@cnmcresearch.org.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Zohn
mesh_terms: D000818:Animals; D019521:Body Patterning; D001846:Bone Development; D002465:Cell Movement; D016764:Cell Polarity; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D051379:Mice; D009154:Mutation / Q000235:genetics; D009432:Neural Crest / Q000166:cytology; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D019170:Somites / Q000166:cytology / Q000196:embryology; D013131:Spine / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051880:Receptors, Notch; C000619976:Supt20 protein, mouse; D014157:Transcription Factors
keywords: Gcn5; Hox code; Somite patterning; Somitogenesis; Supt20