A novel family of T-box genes in urodele amphibian limb development and regeneration: candidate genes involved in vertebrate forelimb/hindlimb patterning.
In certain urodeles, a lost appendage, including hand and foot, can be completely replaced through epimorphic regeneration. The regeneration process involves cellular activities similar to those described for embryogenesis. Working on the assumption that the morphological pattern specific for a forelimb or a hindlimb is controlled by different gene activities in the two limbs, we employed a mRNA differential display screen for the detection of candidate limb identity genes. Using this approach, we have isolated a newt gene which in regenerating and developing limbs reveals properties expected of a gene having a role in controlling limb morphology: (1) it is exclusively expressed in the forelimbs, but not hindlimbs, (2) during embryonic development its expression is co-incident with forelimb bud formation, (3) it has an elevated message level throughout the undifferentiated limb bud and the blastema, respectively, and (4) it is expressed only in mesenchymal, but not in epidermal tissues. This novel newt gene shares a conserved DNA-binding domain, the T-box, with putative transcription factors including the Brachyury (T) gene product. In a following PCR-based screen, we used the evolutionarily conserved T-box motif and amplified a family of related genes in the newt; their different expression patterns in normal and regenerating forelimbs, hindlimbs and tail suggest, in general, an important role of T-domain proteins in vertebrate pattern formation.
Simon
H G
HG
Department of Molecular Genetics and Cell Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. Simon#m#_Hans-Georg@msmail.bms.com
Kittappa
R
R
Khan
P A
PA
Tsilfidis
C
C
Liversage
R A
RA
Oppenheimer
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D019521:Body Patterning / Q000235:genetics*; D003001:Cloning, Molecular / Q000379:methods; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000145:classification / Q000235:genetics*; D005552:Forelimb / Q000254:growth & development*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration / Q000235:genetics*; D012455:Salamandridae / Q000235:genetics* / Q000254:growth & development; D017386:Sequence Homology, Amino Acid; D020825:T-Box Domain Proteins; D014018:Tissue Distribution
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; C105237:Tbox1 protein, Newt