GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search

Koziel, L, Wuelling, M, Schneider, S and Vortkamp, A (2005) Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation. Development 132:5249-60


During endochondral ossification, the secreted growth factor Indian hedgehog (Ihh) regulates several differentiation steps. It interacts with a second secreted factor, parathyroid hormone-related protein (PTHrP), to regulate the onset of hypertrophic differentiation, and it regulates chondrocyte proliferation and ossification of the perichondrium independently of PTHrP. To investigate how the Ihh signal is translated in the different target tissues, we analyzed the role of the zinc-finger transcription factor Gli3, which acts downstream of hedgehog signals in other organs. Loss of Gli3 in Ihh mutants restores chondrocyte proliferation and delays the accelerated onset of hypertrophic differentiation observed in Ihh-/- mutants. Furthermore the expression of the Ihh target genes patched (Ptch) and PTHrP is reactivated in Ihh-/-;Gli3-/- mutants. Gli3 seems thus to act as a strong repressor of Ihh signals in regulating chondrocyte differentiation. In addition, loss of Gli3 in mice that overexpress Ihh in chondrocytes accelerates the onset of hypertrophic differentiation by reducing the domain and possibly the level of PTHrP expression. Careful analysis of chondrocyte differentiation in Gli3-/- mutants revealed that Gli3 negatively regulates the differentiation of distal, low proliferating chondrocytes into columnar, high proliferating cells. Our results suggest a model in which the Ihh/Gli3 system regulates two distinct steps of chondrocyte differentiation: (1) the switch from distal into columnar chondrocytes is repressed by Gli3 in a PTHrP-independent mechanism; (2) the transition from proliferating into hypertrophic chondrocytes is regulated by Gli3-dependent expression of PTHrP. Furthermore, by regulating distal chondrocyte differentiation, Gli3 seems to position the domain of PTHrP expression.


PubMed Online version:10.1242/dev.02097


Animals; Cell Differentiation; Cell Enlargement; Cell Proliferation; Chondrocytes/cytology; Gene Expression Regulation; Hedgehog Proteins; Intracellular Signaling Peptides and Proteins/genetics; Kruppel-Like Transcription Factors/physiology; Membrane Proteins/genetics; Mice; Mice, Transgenic; Mutation; Nerve Tissue Proteins/physiology; Parathyroid Hormone-Related Protein/genetics; Receptors, Cell Surface; Repressor Proteins/physiology; Trans-Activators/genetics; Trans-Activators/physiology



Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status

See also


See Help:References for how to manage references in GONUTS.