First published online August 24, 2007
Development 134, 1804e (2007)
© The Company of Biologists Limited
Sulfs set heparan sulfate code
Heparan sulfate (HS) regulates several extracellular signalling pathways
during development, such as the FGF and Wnt pathways. The binding of HS to
these ligands and their receptors is regulated by its precise 6-O-sulfated
structure, but what controls this `HS code' and thus the signalling functions
of HS? On p. 3327, Ai
and colleagues provide the first evidence that the extracellular HS
6-O-endosulfatases SULF1 and SULF2 are essential in vivo regulators of
HS-mediated developmental signalling. The researchers identify an oesophageal
primary neuronal innervation defect in Sulf1-/-
Sulf2-/- double-null mice and show that aberrant glial cell
line-derived neurotrophic factor (GDNF) signalling causes this defect. Other
experiments indicate that SULF1 and SULF2 are expressed in the developing
oesophagus, that they function redundantly as the major regulators of HS
6-O-desulfation, and that Sulf activity decreases GDNF binding to HS (GDNF
binds to HS through its 6-O-sulfate groups). The researchers conclude,
therefore, that Sulf activity enhances GDNF signalling in normal mice,
consequently promoting neurite sprouting in the embryonic oesophagus.
Related articles in Development:
- SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation
- Xingbin Ai, Toshio Kitazawa, Anh-Tri Do, Marion Kusche-Gullberg, Patricia A. Labosky, and Charles P. Emerson, Jr
Development 2007 134: 3327-3338.
[Abstract]
[Full Text]
