Constitutive activation of sonic hedgehog signaling in the chicken mutant talpid(2): Shh-independent outgrowth and polarizing activity.
We have examined the developmental properties of the polydactylous chicken mutant, talpid(2). Ptc, Gli1, Bmp2, Hoxd13, and Fgf4 are expressed throughout the anteroposterior axis of the mutant limb bud, despite normal Shh expression. The expression of Gli3, Ihh, and Dhh appears to be normal, suggesting that the Shh signaling pathway is constitutively active in talpid(2) mutants. We show that preaxial talpid(2) limb bud mesoderm has polarizing activity in the absence of detectable Shh mRNA. When the postaxial talpid(2) limb bud (including all Shh-expressing cells) is removed, the preaxial cells reform a normal-shaped talpid(2) limb bud (regulate). However, a Shh-expressing region (zone of polarizing activity) does not reform; nevertheless Fgf4 expression in the apical ectodermal ridge is maintained. Such reformed talpid(2) limb buds develop complete talpid(2) limbs. After similar treatment, normal limb buds downregulate Fgf4, the preaxial cells do not regulate, and a truncated anteroposterior deficient limb forms. In talpid(2) limbs, distal outgrowth is independent of Shh and correlates with Fgf4, but not Fgf8, expression by the apical ectodermal ridge. We propose a model for talpid(2) in which leaky activation of the Shh signaling pathway occurs in the absence of Shh ligand.
Caruccio
N C
NC
Department of Anatomy, University of Wisconsin at Madison, Madison, Wisconsin, 53706, USA.
Martinez-Lopez
A
A
Harris
M
M
Dvorak
L
L
Bitgood
J
J
Simandl
B K
BK
Fallon
J F
JF
D000818:Animals; D019521:Body Patterning; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000378:metabolism; D002642:Chick Embryo; D005121:Extremities / Q000033:anatomy & histology / Q000196:embryology; D051519:Fibroblast Growth Factor 4; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000378:metabolism; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000032:analysis; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D008954:Models, Biological; D016296:Mutagenesis; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013997:Time Factors; D016378:Tissue Transplantation; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D051519:Fibroblast Growth Factor 4; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors