Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway.
talpid3 is an embryonic-lethal chicken mutation in a molecularly un-characterised autosomal gene. The recessive, pleiotropic phenotype includes polydactylous limbs with morphologically similar digits. Previous analysis established that hox-D and bmp genes, that are normally expressed posteriorly in the limb bud in response to a localised, posterior source of Sonic Hedgehog (Shh) are expressed symmetrically across the entire anteroposterior axis in talpid3 limb buds. In contrast, Shh expression itself is unaffected. Here we examine expression of patched (ptc), which encodes a component of the Shh receptor, and is probably itself a direct target of Shh signalling, to establish whether talpid3 acts in the Shh pathway. We find that ptc expression is significantly reduced in talpid3 embryos. We also demonstrate that talpid3 function is not required for Shh signal production but is required for normal response to Shh signals, implicating talpid3 in transduction of Shh signals in responding cells. Our analysis of expression of putative components of the Shh pathway, gli1, gli3 and coupTFII shows that genes regulated by Shh are either ectopically expressed or no longer responsive to Shh signals in talpid3 limbs, suggesting possible bifurcation in the Shh pathway. We also describe genetic mapping of gli1, ptc, shh and smoothened in chickens and confirm by co-segregation analysis that none of these genes correspond to talpid3.
Lewis
K E
KE
Developmental Genetics Programme, Krebs Institute, University of Sheffield, Sheffield, S10 2TN, UK.
Drossopoulou
G
G
Paton
I R
IR
Morrice
D R
DR
Robertson
K E
KE
Burt
D W
DW
Ingham
P W
PW
Tickle
C
C
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D051836:COUP Transcription Factors; D002642:Chick Embryo; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D018878:Limb Buds / Q000196:embryology; D008565:Membrane Proteins; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D000072079:Patched Receptors; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D011987:Receptors, Steroid; D015398:Signal Transduction; D016378:Tissue Transplantation; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta; D000071676:Zinc Finger Protein GLI1
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D015513:Oncogene Proteins; D000072079:Patched Receptors; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011987:Receptors, Steroid; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000071676:Zinc Finger Protein GLI1