First published online November 9, 2007
Development 134, 2301e (2007)
© The Company of Biologists Limited
Heparanase releases and primes FGF10 for action
Heparan sulfate (HS) proteoglycans (for example, perlecan) are involved in
many developmental processes, particularly those regulated by fibroblast
growth factors (FGFs). HS regulates FGF activity by acting as an FGF
co-receptor at the cell surface and as an FGF reservoir in the extracellular
matrix. FGF10 signalling is critical for salivary gland development in mammals
and now, on p. 4177,
Matthew Hoffman and colleagues report that the cleavage of perlecan by
heparanase modulates FGF10 activity during branching morphogenesis in the
mouse submandibular gland (SMG). They show that the inhibition of heparanase
in organ culture decreases SMG branching and that the addition of FGF10, but
not other FGFs, rescues branching. Heparanase, they report, releases FGF10
from the basement membrane, where it binds to perlecan. Importantly, the HS
fragment that heparanase releases from perlecan also increases FGF10's
bioactivity, which increases branching complexity in the SMG. Thus,
heparanase, by releasing an HS fragment and FGF10 from the basement membrane,
plays a key role in salivary gland development.
Related articles in Development:
- Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis
- Vaishali N. Patel, Sarah M. Knox, Karen M. Likar, Colin A. Lathrop, Rydhwana Hossain, Siavash Eftekhari, John M. Whitelock, Michael Elkin, Israel Vlodavsky, and Matthew P. Hoffman
Development 2007 134: 4177-4186.
[Abstract]
[Full Text]
