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 polarising region. One candidate is Sonic hedgehog (Shh) protein, but it is not clear whether Shh acts long or short range or via Bmps. Here we dissect the relationship between Shh and Bmp signalling. We show that Shh is necessary not only for initiating bmp2 expression but also for sustaining its expression during the period when additional digits are being specified. We also show that we can reproduce much of the effect of Shh during this period by applying only Bmp2. We further demonstrate that it is Bmps that are responsible for digit specification by transiently adding Noggin or Bmp antibodies to limbs treated with Shh. In such limbs, multiple additional digits still form but they all have the same identity. We also explored time dependency and range of Shh signalling by examining ptc expression. We show that high-level ptc expression is induced rapidly when either Shh beads or polarising regions are grafted to a host limb. Furthermore, we find that high-level ptc 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 initially acts long range to prime the region of the limb competent to form digits and thus control digit number. Then later, Shh acts short range to induce expression of Bmps, whose morphogenetic action specifies digit identity.
A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling
G. Drossopoulou, K.E. Lewis, J.J. Sanz-Ezquerro, N. Nikbakht, A.P. McMahon, C. Hofmann, C. Tickle; A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling. Development 1 April 2000; 127 (7): 1337–1348. doi: https://doi.org/10.1242/dev.127.7.1337
Download citation file:
Advertisement
Cited by
Pathway to Independence programme

We’re excited to announce our new Pathway to Independence programme, aimed at supporting postdocs as they go on the job market. Find out more about the scheme in our Editorial.
Call for papers: Metabolic and Nutritional Control of Development and Regeneration

We are welcoming submissions for our next special issue, which will focus on metabolic and nutritional control of development and regeneration. Submission deadline: 15 May 2023.
Webinar: Increasing the visibility and impact of your research
-HUBSwebinar.jpg?versionId=4486)
Would you like to increase the visibility and impact of your research and raise your profile internationally? If so, register for the very practical webinar we are running in association with HUBS on 23 February 2023.
Transitions in development: Daniel Grimes

Daniel Grimes’s lab studies the consequences of ciliary mutations, including left-right patterning defects and scoliosis. We interviewed Daniel to find out more about his career path, his experience of becoming a group leader and the influence of Jurassic Park.
Preprints in Development
(update)-InPreprints.png?versionId=4486)
As part of our efforts to support the use of preprints and help curate the preprint literature, we are delighted to launch a new article type: ‘In preprints’. These pieces will discuss one or more recent preprints and place them in a broader context.