First published online December 8, 2004
Development 132, 104e (2005)
© The Company of Biologists Limited
Antagonising hedgehog gradients
The morphogen gradients that underpin tissue patterning are often regulated
by negative feedback in which the morphogen upregulates the expression of
inhibitors that attenuate morphogen signalling. Jeong and McMahon now report
that the hedgehog (Hh) antagonists patched 1 (Ptch1) and hedgehog-interacting
protein 1 (Hhip1), both of which are upregulated by Hh signalling,
synergistically regulate growth and patterning in the mouse neural tube (see
p. 143). Ptch1 induces
the rapid endocytosis and degradation of sonic hedgehog (Shh), which controls
patterning in the mammalian spinal cord; Hhip1 sequesters Shh at the cell
surface. The researchers show that mouse embryos lacking both Ptch1
and Hhip1 activities have severe neural tube patterning defects that
are consistent with an increased magnitude and range of Hh signalling. This
and other results indicate that, as in flies, Ptch1 helps to control
Hh gradients through ligand-dependent antagonism. However, in mice, this role
is shared with
Hhip1.
Related articles in Development:
- Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1
- Juhee Jeong and Andrew P. McMahon
Development 2005 132: 143-154.
[Abstract]
[Full Text]
