title: Temporal requirement for bone morphogenetic proteins in regeneration of the tail and limb of Xenopus tadpoles.
abstract: Bone morphogenetic protein (BMP) signalling is necessary for both the development of the tail bud and for tail regeneration in Xenopus laevis tadpoles. Using a stable transgenic line in which expression of the soluble BMP inhibitor noggin is under the control of the temperature inducible hsp70 promoter, we have investigated the timing of the requirement for BMP signalling during tail regeneration. If noggin expression is induced followed by partial amputation of the tail, then wound closure and the formation of the neural ampulla occur normally but outgrowth of the regeneration bud is inhibited. Furthermore, we show that BMP signalling is also necessary for limb bud regeneration, which occurs in Xenopus tadpoles prior to differentiation. When noggin expression is induced, limb bud regeneration fails at an early stage and a stump is formed. The situation appears similar to the tail, with formation of the limb bud blastema occurring but renewed outgrowth inhibited. The transcriptional repressor Msx1, a direct target of BMP signalling with known roles in vertebrate appendage regeneration, fails to be re-expressed in both tail and limb in the presence of noggin. DNA labelling studies show that proliferation in the notochord and spinal cord of the tail, and of the blastema in the limb bud, is significantly inhibited by noggin induction, suggesting that in the context of these regenerating appendages BMP is mainly required, directly or indirectly, as a mitogenic factor.
authors.affiliation: Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Beck
authors.forename: Bea
authors.initials: B
authors.lastname: Christen
authors.forename: Donna
authors.initials: D
authors.lastname: Barker
authors.forename: Jonathan M W
authors.initials: JM
authors.lastname: Slack
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D005121:Extremities; D015870:Gene Expression; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000502:physiology; D008322:Mammals; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013623:Tail; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D051957:MSX1 Transcription Factor; D029867:Xenopus Proteins; D000099176:Noggin Protein; C504610:Bmp2 protein, Xenopus; C497996:MSX1 protein, Xenopus; C525812:bmp4 protein, Xenopus