ArticleThe Journal of biological chemistry2010
Inactivation of Patched1 in the mouse limb has novel inhibitory effects on the chondrogenic program.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia.Bone research · 2022Article
- Tbx4 function during hindlimb development reveals a mechanism that explains the origins of proximal limb defects.Development (Cambridge, England) · 2021Article
- Wdpcp regulates cellular proliferation and differentiation in the developing limb via hedgehog signaling.BMC developmental biology · 2021Article
- Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate.International journal of molecular sciences · 2019Review
- Article
- Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease.Nature genetics · 2017Article
- Gene expression profile in human induced pluripotent stem cells: Chondrogenic differentiation in vitro, part B.Molecular medicine reports · 2017Article
- CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs cartilage in mice with destabilized medial meniscus.Stem cell research & therapy · 2017Article
- CK2.1, a novel peptide, induces articular cartilage formation in vivo.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017Article
- Review
- Loss of jab1 in osteochondral progenitor cells severely impairs embryonic limb development in mice.Journal of cellular physiology · 2014Article
- The Ptch1(DL) mouse: a new model to study lambdoid craniosynostosis and basal cell nevus syndrome-associated skeletal defects.Genesis (New York, N.Y. : 2000) · 2013Article
- Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma.Nature genetics · 2013Article
- Compensatory regulation of the Snai1 and Snai2 genes during chondrogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Article
- Essential developmental, genomic stability, and tumour suppressor functions of the mouse orthologue of hSSB1/NABP2.PLoS genetics · 2013Article
- Ihh and Runx2/Runx3 signaling interact to coordinate early chondrogenesis: a mouse model.PloS one · 2013Article
- Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies.Human molecular genetics · 2012Article
- Pleiotropic patterning response to activation of Shh signaling in the limb apical ectodermal ridge.Developmental dynamics : an official publication of the American Association of Anatomists · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bones of the vertebrate limb form by the process of endochondral ossification, whereby limb mesenchyme condenses to form an intermediate cartilage scaffold that is then replaced by bone. Although Indian hedgehog (IHH) is known to control hypertophic differentiation of chondrocytes during this process, the role of hedgehog signaling in the earlier stages of chondrogenesis is less clear. We have conditionally inactivated the hedgehog receptor Ptc1 in undifferentiated limb mesenchyme of the mouse limb using Prx1-Cre, thus inducing constitutively active ligand-independent hedgehog signaling. In addition to major patterning defects, we observed a marked disruption to the cartilage elements in the limbs of Prx1-Cre:Ptc1(c/c) embryos. Using an in vitro micromass culture system we show that this defect lies downstream of mesenchymal cell condensation and likely upstream of chondrocyte differentiation. Despite early increases in levels of chondrogenic genes, soon after mesenchymal condensation the stromal layer of Prx1-Cre:Ptc1(c/c)-derived micromass cultures is characterized by a loss of cell integrity, which is associated with increased cell death and a striking decrease in Alcian blue staining cartilage nodules. Furthermore, inhibition of the hedgehog pathway activation using cyclopamine was sufficient to essentially overcome this chondrogenic defect in both micromass and ex vivo explant assays of Prx1-Cre:Ptc1(c/c) limbs. These data demonstrate for the first time the inhibitory effect of cell autonomously activated hedgehog signaling on chondrogenesis, and stress the importance of PTC1 in maintaining strict control of signaling levels during this phase of skeletal development.
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