G. Drossopoulou et al., A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling, DEVELOPMENT, 127(7), 2000, pp. 1337-1348
It has been proposed that digit identity in chick limb bud is specified in
a dose-dependent fashion by a long-range morphogen, produced by the polaris
ing region. One candidate is Sonic hedgehog (Shh) protein, but it is not cl
ear whether Shh acts long or short range or via Bmps. Here we dissect the r
elationship between Shh and Bmp signalling. We show that Shh is necessary n
ot only for initiating bmp2 expression but also for sustaining its expressi
on during the period when additional digits are being specified. We also sh
ow that we can reproduce much of the effect of Shh during this period by ap
plying only Bmp2. We further demonstrate that it is Bmps that are responsib
le for digit specification by transiently adding Noggin or Bmp antibodies t
o limbs treated with Shh. In such limbs, multiple additional digits still f
orm but they all have the same identity. We also explored time dependency a
nd range of Shh signalling by examining pre expression. We show that high-l
evel ptc expression is induced rapidly when either Shh beads or polarising
regions are grafted to a host limb. Furthermore, we find that high-level pt
c expression is first widespread but later more restricted. All these data
lead us to propose a new model for digit patterning. We suggest that Shh in
itially acts long range to prime the region of the limb competent to form d
igits and thus control digit number. Then later, Shh acts short range to in
duce expression of Bmps, whose morphogenetic action specifies digit identit
y.