title: A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling.
abstract: 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.
authors.affiliation: Department of Anatomy and Physiology, The Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
authors.forename: G
authors.initials: G
authors.lastname: Drossopoulou
authors.forename: K E
authors.initials: KE
authors.lastname: Lewis
authors.forename: J J
authors.initials: JJ
authors.lastname: Sanz-Ezquerro
authors.forename: N
authors.initials: N
authors.lastname: Nikbakht
authors.forename: A P
authors.initials: AP
authors.lastname: McMahon
authors.forename: C
authors.initials: C
authors.lastname: Hofmann
authors.forename: C
authors.initials: C
authors.lastname: Tickle
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002642:Chick Embryo; D005121:Extremities / Q000196:embryology*; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D000072079:Patched Receptors; D011506:Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014921:Wings, Animal / Q000196:embryology
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D016212:Transforming Growth Factor beta