Constitutive activation of sonic hedgehog signaling in the chicken mutant talpid(2): Shh-independent outgrowth and polarizing activity
| Autor: | John F. Fallon, Leah Dvorak, Nicholas C. Caruccio, A Martinez-Lopez, B K Simandl, J. J. Bitgood, Matthew P. Harris |
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| Rok vydání: | 1999 |
| Předmět: |
Apical ectodermal ridge
Time Factors apical ectodermal ridge Gli1 Bone Morphogenetic Protein 2 Chick Embryo Gli3 Mesoderm 0302 clinical medicine Transforming Growth Factor beta patched In Situ Hybridization 0303 health sciences Hedgehog signaling pathway Cell biology medicine.anatomical_structure embryonic structures Bone Morphogenetic Proteins Tissue Transplantation signaling Signal Transduction medicine.medical_specialty animal structures Fibroblast Growth Factor 8 Fibroblast Growth Factor 4 Biology Models Biological 03 medical and health sciences Limb bud FGF8 Internal medicine Proto-Oncogene Proteins GLI3 medicine Limb development Animals Hedgehog Proteins RNA Messenger Molecular Biology 030304 developmental biology Body Patterning Homeodomain Proteins zone of polarizing activity Proteins Extremities Cell Biology talpid2 body regions Fibroblast Growth Factors Endocrinology Zone of polarizing activity Mutagenesis limb development Hoxd13 Trans-Activators 030217 neurology & neurosurgery Hedgehog Developmental Biology Transcription Factors |
| Zdroj: | Developmental biology. 212(1) |
| ISSN: | 0012-1606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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