Regulation of vertebral column development by Pax1

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861186
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto University
• Principal Investigator: Takimoto Aki 京都大学, 健康長寿社会の総合医療開発ユニット, 助教 (00378902)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 転写制御 / 組織形成 / 椎間板 / 軟骨

Outline of Final Research Achievements

Pax1 is a paired-box-containing transcription factor that is expressed in the sclerotome of developing axial skeleton. As cartilage formation proceeds, Pax1 expression is downregulated in the cartilage and its transcripts become localized to the annulus fibrosus of intervertebral discs (IVDs). This study aims to investigate target genes of Pax1 in IVDs and the potential role of Pax1 during vertebral column development. In the annulus fibrosus cells, knockdown of Pax1 using siRNA resulted in the upregulation of certain cartilage matrix genes. Chromatin-immunoprecipitation and gel shift assays revealed a novel Pax1-binding site present in the enhancer element of cartilage matrix gene. These results suggest that Pax1 negatively regulates the expression of cartilage matrix gene via a competitive binding to its enhancer element in IVD cells, which may contribute to the establishment of cartilaginous and non-cartilaginous tissue boundaries during vertebral column formation.

Free Research Field

発生学