デジマ カツフミ   Dejima Katsufumi
  出嶋 克史
   所属   医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Glypicans regulate JAK/STAT signaling and distribution of the Unpaired morphogen.
掲載誌名 正式名:Development (Cambridge, England)
略  称:Development
ISSNコード:1477-9129(Electronic)0950-1991(Linking)
巻・号・頁 139(22),4162-71頁
著者・共著者 Hayashi Yoshiki, Sexton Travis R, Dejima Katsufumi, Perry Dustin W, Takemura Masahiko, Kobayashi Satoru, Nakato Hiroshi, Harrison Douglas A
発行年月 2012/11
概要 In Drosophila, ligands of the Unpaired (Upd) family activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The JAK/STAT pathway controls many developmental events, including multiple functions in the ovary. These include an early role in the germarium for specification of stalk cells and a later role in the vitellarium to pattern the follicular epithelium surrounding each cyst. In this latter role, graded JAK/STAT activation specifies three distinct anterior follicular cell fates, suggesting that Upd is a morphogen in this system. Consistent with the JAK/STAT activation pattern in the vitellarium, Upd forms a concentration gradient on the apical surface of the follicular epithelium with a peak at its source, the polar cells. Like many morphogens, signaling and distribution of Upd are regulated by the heparan sulfate proteoglycans (HSPGs) Dally and Dally-like. Mutations in these glypican genes and in heparan sulfate biosynthetic genes result in disruption of JAK/STAT signaling, loss or abnormal formation of the stalk and significant reduction in the accumulation of extracellular Upd. Conversely, forced expression of Dally causes ectopic accumulation of Upd in follicular cells. Furthermore, biochemical studies reveal that Upd and Dally bind each other on the surface of the cell membrane. Our findings demonstrate that Drosophila glypicans regulate formation of the follicular gradient of the Upd morphogen, Upd. Furthermore, we establish the follicular epithelium as a new model for morphogen signaling in complex organ development.
DOI 10.1242/dev.078055
文献番号 23093424