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Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity.
- Source :
-
Nature [Nature] 2002 Aug 29; Vol. 418 (6901), pp. 979-83. Date of Electronic Publication: 2002 Aug 18. - Publication Year :
- 2002
-
Abstract
- Most current models propose Sonic hedgehog (Shh) as the primary determinant of anteroposterior development of amniote limbs. Shh protein is said to be required to direct the formation of skeletal elements and to specify digit identity through dose-dependent activation of target gene expression. However, the identity of genes targeted by Shh, and the regulatory mechanisms controlling their expression, remain poorly understood. Gli3 (the gene implicated in human Greig cephalopolysyndactyly syndrome) is proposed to negatively regulate Shh by restricting its expression and influence to the posterior mesoderm. Here we report genetic analyses in mice showing that Shh and Gli3 are dispensable for formation of limb skeletal elements: Shh(-/-) Gli3(-/-) limbs are distally complete and polydactylous, but completely lack wild-type digit identities. We show that the effects of Shh signalling on skeletal patterning and ridge maintenance are necessarily mediated through Gli3. We propose that the function of Shh and Gli3 in limb skeletal patterning is limited to refining autopodial morphology, imposing pentadactyl constraint on the limb's polydactyl potential, and organizing digit identity specification, by regulating the relative balance of Gli3 transcriptional activator and repressor activities.
- Subjects :
- Animals
Blotting, Western
Body Patterning
DNA-Binding Proteins genetics
Extremities physiology
Gene Deletion
Gene Expression Regulation, Developmental
Hedgehog Proteins
In Situ Hybridization
Kruppel-Like Transcription Factors
Leg Bones metabolism
Limb Buds embryology
Limb Buds metabolism
Mice
Mice, Knockout
Morphogenesis
RNA, Messenger genetics
RNA, Messenger metabolism
Signal Transduction
Trans-Activators genetics
Transcription Factors genetics
Zinc Finger Protein Gli3
DNA-Binding Proteins metabolism
Extremities embryology
Leg Bones embryology
Nerve Tissue Proteins
Trans-Activators metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 418
- Issue :
- 6901
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 12198547
- Full Text :
- https://doi.org/10.1038/nature01033