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The vertebrate limb is one of the most intensively studied organs in the field of developmental biology. Limb development in tetrapod vertebrates is highly conserved and dependent on the interaction of several important molecular pathways. The bone morphogenetic protein (BMP) signaling cascade is one of these pathways and has been shown to be crucial for several aspects of limb development. Here, we have used a Xenopus laevis transgenic line, in which expression of the inhibitor Noggin is under the control of the heat-shock promoter hsp70 to examine the effects of attenuation of BMP signaling at different stages of limb development. Remarkably different phenotypes were produced at different stages, illustrating the varied roles of BMP in development of the limb. Very early limb buds appeared to be refractory to the effects of BMP attenuation, developing normally in most cases. Ectopic limbs were produced by overexpression of Noggin corresponding to a brief window of limb development at about stage 49/50, as recently described by Christen et al. (2012). Attenuation of BMP signaling in stage 51 or 52 tadpoles lead to a reduction in the number of digits formed, resulting in hypodactyly or ectrodactyly, as well as occasional defects in the more proximaltibia-fibula. Finally, inhibition at stage 54 (paddle stage) led to the formation of dramatically shortened digits resulting from loss of distal phalanges. Transcriptome analysis has revealed the possibility that more Noggin-sensitive members of the BMP family could be involved in limb development than previously suspected. Our analysis demonstrates the usefulness of heat-shock-driven gene expression as an effective method for inhibiting a developmental pathway at different times during limb development.
Abu-Daya,
The secreted integrin ligand nephronectin is necessary for forelimb formation in Xenopus tropicalis.
2011, Pubmed,
Xenbase
Abu-Daya,
The secreted integrin ligand nephronectin is necessary for forelimb formation in Xenopus tropicalis.
2011,
Pubmed
,
Xenbase Akiyama,
The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.
2002,
Pubmed Akiyama,
Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice.
2007,
Pubmed Altabef,
Dorso-ventral ectodermal compartments and origin of apical ectodermal ridge in developing chick limb.
1997,
Pubmed Bandyopadhyay,
Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis.
2006,
Pubmed Barker,
Overexpression of the transcription factor Msx1 is insufficient to drive complete regeneration of refractory stage Xenopus laevis hindlimbs.
2009,
Pubmed
,
Xenbase Beck,
Temporal requirement for bone morphogenetic proteins in regeneration of the tail and limb of Xenopus tadpoles.
2006,
Pubmed
,
Xenbase Beck,
Analysis of the developing Xenopus tail bud reveals separate phases of gene expression during determination and outgrowth.
1998,
Pubmed
,
Xenbase Beck,
Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate.
2003,
Pubmed
,
Xenbase Bell,
SOX9 directly regulates the type-II collagen gene.
1997,
Pubmed Bénazet,
Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.
2009,
Pubmed Bénazet,
A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning.
2009,
Pubmed Capdevila,
Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin.
1999,
Pubmed Chiang,
Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function.
2001,
Pubmed Christen,
All limbs are not the same.
1998,
Pubmed
,
Xenbase Christen,
Regeneration-specific expression pattern of three posterior Hox genes.
2003,
Pubmed
,
Xenbase Christen,
Transient downregulation of Bmp signalling induces extra limbs in vertebrates.
2012,
Pubmed
,
Xenbase Christen,
FGF-8 is associated with anteroposterior patterning and limb regeneration in Xenopus.
1997,
Pubmed
,
Xenbase Cohn,
Fibroblast growth factors induce additional limb development from the flank of chick embryos.
1995,
Pubmed Conesa,
Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research.
2005,
Pubmed Dahn,
Interdigital regulation of digit identity and homeotic transformation by modulated BMP signaling.
2000,
Pubmed Dathe,
Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2.
2009,
Pubmed DENT,
Limb regeneration in larvae and metamorphosing individuals of the South African clawed toad.
1962,
Pubmed Francis,
Bone morphogenetic proteins and a signalling pathway that controls patterning in the developing chick limb.
1994,
Pubmed Galli,
Distinct roles of Hand2 in initiating polarity and posterior Shh expression during the onset of mouse limb bud development.
2010,
Pubmed Grabherr,
Full-length transcriptome assembly from RNA-Seq data without a reference genome.
2011,
Pubmed Khokha,
Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning.
2003,
Pubmed
,
Xenbase Laufer,
Expression of Radical fringe in limb-bud ectoderm regulates apical ectodermal ridge formation.
1997,
Pubmed Lehmann,
Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.
2003,
Pubmed Lehmann,
A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN.
2007,
Pubmed Lewandoski,
Fgf8 signalling from the AER is essential for normal limb development.
2000,
Pubmed McEwan,
Expression of key retinoic acid modulating genes suggests active regulation during development and regeneration of the amphibian limb.
2011,
Pubmed
,
Xenbase Moon,
Fgf8 is required for outgrowth and patterning of the limbs.
2000,
Pubmed Mortlock,
The molecular basis of hypodactyly (Hd): a deletion in Hoxa 13 leads to arrest of digital arch formation.
1996,
Pubmed Newman,
Thiosemicarbazide-induced osteolathyrism in metamorphosing Xenopus laevis.
1983,
Pubmed
,
Xenbase Ovchinnikov,
BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning.
2006,
Pubmed Pizette,
BMP controls proximodistal outgrowth, via induction of the apical ectodermal ridge, and dorsoventral patterning in the vertebrate limb.
2001,
Pubmed Plöger,
Brachydactyly type A2 associated with a defect in proGDF5 processing.
2008,
Pubmed Post,
Severe limb defects in Hypodactyly mice result from the expression of a novel, mutant HOXA13 protein.
2000,
Pubmed Retting,
BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation.
2009,
Pubmed Riddle,
Sonic hedgehog mediates the polarizing activity of the ZPA.
1993,
Pubmed Robertson,
Cellular analysis of limb development in the mouse mutant hypodactyly.
1996,
Pubmed Satoh,
Characterization of Xenopus digits and regenerated limbs of the froglet.
2006,
Pubmed
,
Xenbase SAUNDERS,
The proximo-distal sequence of origin of the parts of the chick wing and the role of the ectoderm.
1948,
Pubmed Seemann,
Mutations in GDF5 reveal a key residue mediating BMP inhibition by NOGGIN.
2009,
Pubmed Stopper,
Of chicken wings and frog legs: a smorgasbord of evolutionary variation in mechanisms of tetrapod limb development.
2005,
Pubmed Summerbell,
A quantitative analysis of the effect of excision of the AER from the chick limb-bud.
1974,
Pubmed Tarchini,
Regulatory constraints in the evolution of the tetrapod limb anterior-posterior polarity.
2006,
Pubmed Temtamy,
Brachydactyly.
2008,
Pubmed Tickle,
Positional signalling and specification of digits in chick limb morphogenesis.
1975,
Pubmed Towers,
Growing models of vertebrate limb development.
2009,
Pubmed Verheyden,
An Fgf/Gremlin inhibitory feedback loop triggers termination of limb bud outgrowth.
2008,
Pubmed Williams,
Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad transcriptional activation functions independent of HOX DNA-binding capability.
2005,
Pubmed Yoon,
Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo.
2005,
Pubmed Zeller,
Vertebrate limb bud development: moving towards integrative analysis of organogenesis.
2009,
Pubmed Zimmerman,
The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4.
1996,
Pubmed
,
Xenbase Zúñiga,
Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds.
1999,
Pubmed
,
Xenbase
