title: Hoxa-5 acts in segmented somites to regulate cervical vertebral morphology.
abstract: The vertebrate axial skeleton (vertebral column and ribs) is derived from embryonic structures called somites. Mechanisms of somite formation and patterning are largely conserved along the length of the body axis, but segments acquire different morphologies in part through the action of Hox transcription factors. Although Hox genes' roles in axial skeletal patterning have been extensively characterized, it is still not well understood how they interact with somite patterning pathways to regulate different vertebral morphologies. Here, we investigated the role of Hoxa-5 in after somite segmentation in chick. Hoxa-5 mRNA is expressed in posterior cervical somites, and within them is restricted mainly to a sub-domain of lateral sclerotome. RNAi-based knockdown leads to cartilage defects in lateral vertebral elements (rib homologous structures) whose morphologies vary within and outside of the Hoxa-5 expression domain. Both knockdown and misexpression suggest that Hoxa-5 acts via negative regulation of Sox-9. Further, Hoxa-5 misexpression suggests that spatial and/or temporal restriction of Hoxa-5 expression is necessary for proper vertebral morphology. Finally, the restriction of Hoxa-5 expression to lateral sclerotome, which we hypothesize is important for its patterning function, involves regulation by signaling pathways that pattern somites, Fgf-8 and Shh.
authors: Department of Biology, Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, USA.
authors: Jessica W
authors: JW
authors: Chen
authors: Soombal
authors: S
authors: Zahid
authors: Meghan H
authors: MH
authors: Shilts
authors: Sara J
authors: SJ
authors: Weaver
authors: Rachel M
authors: RM
authors: Leskowitz
authors: Samima
authors: S
authors: Habbsa
authors: Danielle
authors: D
authors: Aronowitz
authors: Karimah P
authors: KP
authors: Rokins
authors: Yvonne
authors: Y
authors: Chang
authors: Zena
authors: Z
authors: Pinnella
authors: Lauren
authors: L
authors: Holloway
authors: Jennifer H
authors: JH
authors: Mansfield
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning; D002356:Cartilage / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D002574:Cervical Vertebrae / Q000196:embryology* / Q000473:pathology*; D002642:Chick Embryo; D002645:Chickens; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis / Q000235:genetics; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D019170:Somites / Q000196:embryology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C070835:PAX1 transcription factor; D051524:Fibroblast Growth Factor 8