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GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis.
- Source :
-
Developmental cell [Dev Cell] 2012 Apr 17; Vol. 22 (4), pp. 837-48. Date of Electronic Publication: 2012 Mar 29. - Publication Year :
- 2012
-
Abstract
- Inactivation of Gli3, a key component of Hedgehog signaling in vertebrates, results in formation of additional digits (polydactyly) during limb bud development. The analysis of mouse embryos constitutively lacking Gli3 has revealed the essential GLI3 functions in specifying the anteroposterior (AP) limb axis and digit identities. We conditionally inactivated Gli3 during mouse hand plate development, which uncoupled the resulting preaxial polydactyly from known GLI3 functions in establishing AP and digit identities. Our analysis revealed that GLI3 directly restricts the expression of regulators of the G(1)-S cell-cycle transition such as Cdk6 and constrains S phase entry of digit progenitors in the anterior hand plate. Furthermore, GLI3 promotes the exit of proliferating progenitors toward BMP-dependent chondrogenic differentiation by spatiotemporally restricting and terminating the expression of the BMP antagonist Gremlin1. Thus, Gli3 is a negative regulator of the proliferative expansion of digit progenitors and acts as a gatekeeper for the exit to chondrogenic differentiation.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biomarkers metabolism
Blotting, Western
Body Patterning
Bone Morphogenetic Proteins genetics
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression Profiling
Gene Expression Regulation, Developmental
Hand Deformities etiology
Limb Buds metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Oligonucleotide Array Sequence Analysis
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
S Phase physiology
Stem Cells metabolism
Zinc Finger Protein Gli3
Bone Morphogenetic Proteins metabolism
Cell Proliferation
Chondrogenesis physiology
Kruppel-Like Transcription Factors physiology
Limb Buds cytology
Nerve Tissue Proteins physiology
Polydactyly pathology
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 22465667
- Full Text :
- https://doi.org/10.1016/j.devcel.2012.01.006