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The heparan sulfate 6-O-endosulfatases sulf1 and sulf2 regulate multiple cellular processes and organ development. Sulfs modulate a range of heparan-sulfate-dependent extracellular pathways, including the fibroblast growth factor, bone morphogenetic protein, and wingless/wnt signaling pathways. Known patterns of sulf transcript expression together with functional experiments have implicated the sulfs in chondrogenesis and muscle regeneration in mammals. Here, we describe the expression patterns of Xenopus laevis sulf1 and sulf2 in developing forelimbs and hindlimbs and demonstrate novel expression of the sulf transcripts in the regenerating hindlimbs, with prominent sulf2 expression in the proliferating blastema and transient expression of sulf1 in the redeveloping apical epidermal ridge. These findings further suggest involvement of the sulfs in successful limb regeneration in amphibians.
Figure 1.
Sulf1 expression in X. laevis stage 51−56 forelimbs (A−E) and stage 51−56 hindlimbs (F−L) examined by a whole mount in situ hybridization. Specific staining is dark purple. Red arrows in the more proximal part indicate gene expression at the putative shoulder/hip and elbow/knee joints; blue arrows indicate expression at the future wrist/ankle joints; yellow arrows indicate transcript expression in the autopod region. Roman numerals indicate digit number. All limbs are oriented proximal to the left and posterior uppermost, with the tadpoles lying on their right side.
Figure 2.
Sulf2 expression in X. laevis stage 51−53 forelimbs (A−C) and stage 50−57 hindlimbs (D−J) examined by a whole mount in situ hybridization. Specific staining is dark purple. Red arrows in the more proximal part indicate gene expression at the putative shoulder/hip and elbow/knee joints; blue arrows indicate expression at the future wrist/ankle joints; yellow arrows indicate transcript expression in the autopod region; empty arrows indicate reduced level of expression. Roman numerals indicate digit number. The boxed region in E indicates area of histological section shown in E′, accompanied by the corresponding schematic (E′) showing area of gene expression in the mesenchyme. All limbs are oriented proximal to the left and posterior uppermost, with the tadpoles lying on their right side. AER, apical epidermal ridge; m, mesenchyme.
Figure 3.
X. laevis sulf1 (A−F) and sulf2 (G−L) expression in regenerating hindlimbs originally operated at developmental stage 52 examined by a whole mount in situ hybridization. Specific staining is dark purple. Black arrows point to regions of transcript expression that is specific to regeneration; empty arrows indicate reduced level of expression. The original site of amputation is indicated by the black dotted line. Boxed region in C and I indicate area of histological section as shown in C′ and I′ respectively, accompanied by their respective schematics. All limbs are oriented proximal to the left and posterior uppermost, with the tadpoles lying on their right side. aec, apical epidermal cap; fa, functional aec; b, blastema.
Ai,
Substrate specificity and domain functions of extracellular heparan sulfate 6-O-endosulfatases, QSulf1 and QSulf2.
2006, Pubmed
Ai,
Substrate specificity and domain functions of extracellular heparan sulfate 6-O-endosulfatases, QSulf1 and QSulf2.
2006,
Pubmed
Ai,
QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling.
2003,
Pubmed
Barker,
Overexpression of the transcription factor Msx1 is insufficient to drive complete regeneration of refractory stage Xenopus laevis hindlimbs.
2009,
Pubmed
,
Xenbase
Beck,
Studying regeneration in Xenopus.
2012,
Pubmed
,
Xenbase
Dhoot,
Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase.
2001,
Pubmed
Freeman,
Extracellular regulation of developmental cell signaling by XtSulf1.
2008,
Pubmed
,
Xenbase
Gorsi,
Tinkering with heparan sulfate sulfation to steer development.
2007,
Pubmed
Hongo,
FGF signaling and the anterior neural induction in Xenopus.
1999,
Pubmed
,
Xenbase
Isaacs,
Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification.
1992,
Pubmed
,
Xenbase
Kirn-Safran,
Multifunctionality of extracellular and cell surface heparan sulfate proteoglycans.
2009,
Pubmed
Kleinschmit,
Drosophila heparan sulfate 6-O endosulfatase regulates Wingless morphogen gradient formation.
2010,
Pubmed
Lamanna,
The heparanome--the enigma of encoding and decoding heparan sulfate sulfation.
2007,
Pubmed
Langsdorf,
Sulfs are regulators of growth factor signaling for satellite cell differentiation and muscle regeneration.
2007,
Pubmed
Maltseva,
The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair.
2013,
Pubmed
McEwan,
Expression of key retinoic acid modulating genes suggests active regulation during development and regeneration of the amphibian limb.
2011,
Pubmed
,
Xenbase
Morimoto-Tomita,
Sulf-2, a proangiogenic heparan sulfate endosulfatase, is upregulated in breast cancer.
2005,
Pubmed
Otsuki,
Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways.
2010,
Pubmed
Pownall,
eFGF, Xcad3 and Hox genes form a molecular pathway that establishes the anteroposterior axis in Xenopus.
1996,
Pubmed
,
Xenbase
Ramsbottom,
Sulf1 influences the Shh morphogen gradient during the dorsal ventral patterning of the neural tube in Xenopus tropicalis.
2014,
Pubmed
,
Xenbase
Ratzka,
Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal development.
2008,
Pubmed
Rosen,
Sulf-2: an extracellular modulator of cell signaling and a cancer target candidate.
2010,
Pubmed
Towers,
Growing models of vertebrate limb development.
2009,
Pubmed
Tran,
Heparan sulfate 6-O-endosulfatases (Sulfs) coordinate the Wnt signaling pathways to regulate myoblast fusion during skeletal muscle regeneration.
2012,
Pubmed
Tran,
Design and use of transgenic reporter strains for detecting activity of signaling pathways in Xenopus.
2014,
Pubmed
,
Xenbase
Turnbull,
Heparan sulfate glycomics: towards systems biology strategies.
2010,
Pubmed
Viviano,
Domain-specific modification of heparan sulfate by Qsulf1 modulates the binding of the bone morphogenetic protein antagonist Noggin.
2004,
Pubmed
Wang,
QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis.
2004,
Pubmed
,
Xenbase
Winterbottom,
Complementary expression of HSPG 6-O-endosulfatases and 6-O-sulfotransferase in the hindbrain of Xenopus laevis.
2009,
Pubmed
,
Xenbase
Wojcinski,
DSulfatase-1 fine-tunes Hedgehog patterning activity through a novel regulatory feedback loop.
2011,
Pubmed
Yan,
Shaping morphogen gradients by proteoglycans.
2009,
Pubmed
Zeller,
Vertebrate limb bud development: moving towards integrative analysis of organogenesis.
2009,
Pubmed
Zhao,
Sulf1 expression pattern and its role in cartilage and joint development.
2006,
Pubmed
