Functional analysis of chick heparan sulfate 6-O-sulfotransferases in limb bud development

Takashi Kobayashi, Hiroko Habuchi, Ken Nogami, Satoko Ashikari-Hada, Koji Tamura, Hiroyuki Ide, Koji Kimata

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Heparan sulfate (HS) interacts with numerous growth factors, morphogens, receptors, and extracellular matrix proteins. Disruption of HS synthetic enzymes causes perturbation of growth factor signaling and malformation in vertebrate and invertebrate development. Our previous studies show that the O-sulfation patterns of HS are essential for the specific binding of growth factors to HS chains, and that depletion of O-sulfotransferases results in remarkable developmental defects in Drosophila, zebrafish, chick, and mouse. Here, we show that inhibition of chick HS-6-O-sulfotransferases (HS6ST-1 and HS6ST-2) in the prospective limb region by RNA interference (RNAi) resulted in the truncation of limb buds and reduced Fgf-8 and Fgf-10 expressions in the apical ectodermal ridge and in the underlying mesenchyme, respectively. HS6ST-2 RNAi resulted in a higher frequency of limb truncation and a more marked change in both Fgf-8 and Fgf-10 expressions than that achieved with HS6ST-1 RNAi. HS6ST-1 RNAi and HS6ST-2 RNAi caused a significant but distinct reduction in the levels of different 6-O-sulfation in HS, possibly as a result of their different substrate specificities. Our data support a model where proper levels and patterns of 6-O-sulfation of HS play essential roles in chick limb bud development.

Original languageEnglish
Pages (from-to)146-156
Number of pages11
JournalDevelopment Growth and Differentiation
Volume52
Issue number2
DOIs
Publication statusPublished - 2010 Feb

Keywords

  • Chick
  • Heparan sulfate
  • Heparan sulfate 6-O-sulfotransferases
  • Limb bud
  • RNAi

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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