Limb chondrogenesis is compromised in the versican deficient hdf mouse

Williams, Denis; Presar, Ashley R.; Richmond, A. Todd; Mjaatvedt, Corey H.; Hoffman, Stanley; Capehart, Anthony A.

doi:10.1016/j.bbrc.2005.06.189

Cited by 36 publications

(35 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, versican binding to other ECM molecules may block neurite adhesion to other permissive matrix substrates such as fibronectin and collagen (Yamagata et al 1989), which, along with versican, are all expressed in incipient limb cartilage tissues (Shinomura et al 1990). As reported previously (Williams et al 2005), in limb cell cultures derived from hdf homozygous mutant embryos, at either 3 or 6 days Type II collagen or versican-positive cartilage foci were not observed (Figure 5f). Cartilage nodules do not differentiate in the versican-deficient hdf mutant in spite of expression of other molecules implicated in chondrogenesis, including fibronectin and cadherins (Williams et al 2005).…”

Section: Resultssupporting

confidence: 86%

“…As reported previously (Williams et al 2005), in limb cell cultures derived from hdf homozygous mutant embryos, at either 3 or 6 days Type II collagen or versican-positive cartilage foci were not observed (Figure 5f). Cartilage nodules do not differentiate in the versican-deficient hdf mutant in spite of expression of other molecules implicated in chondrogenesis, including fibronectin and cadherins (Williams et al 2005). The defect in the chondrogenic pathway appears to reside in lack of mesenchymal aggregation along a wild type time course, suggesting an interactive role between mature versican proteoglycan and other molecules in this process.…”

Section: Resultssupporting

confidence: 86%

“…Its function has been linked to cartilage differentiation Shinomura et al 1990), cell proliferation (Zhang et al 1999;Yang et al 2003), and tissue patterning (Chalepakis et al 1993;Harris and Jahoda, 2001). The recent availability of the heart defect (hdf) mutant mouse (Zhang et al 1994), which bears an embryonic homozygous lethal mutation of Cspg2 encoding the core protein of versican (Mjaatvedt et al 1998), has shown that expression of the mature versican proteoglycan is pivotal to limb chondrogenesis (Williams et al 2005).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neural Tissue Co-Culture with Mesenchyme to Investigate Patterningof Peripheral Nerve During Murine Embryonic Limb Development

et al. 2004

Self Cite

View full text Add to dashboard Cite

Lateral plate mesoderm is native to the developing limb while other cells such as neurons extend migratory axonal processes from the neural tube. Questions regarding how axons migrate to their proper location in the developing limb remain unanswered. Extracellular matrix molecules expressed in developing limb cartilages, such as the versican proteoglycan, may function as inhibitory cues to nerve migration, thus facilitating its proper patterning. In the present study, a method is described for co-culture of neural tissue with high density micromass preparations of mouse limb mesenchyme in order to investigate neurite patterning during limb chondrogenesis in vitro. Comparison of hdf (heart defect) mouse limb mesenchyme, which bears an insertional mutation in the versican proteoglycan core protein, with wild type demonstrated that the described technique provides a useful method for transgenic analysis in studies of chondrogenic regulation of neurite patterning. Differentiating wild type limb mesenchyme expressed cartilage characteristic Type II collagen and versican at 1 day and exhibited numerous well defined cartilage foci by 3 days. Wild type neurites extended into central regions of host cultures between 3 and 6 days and consistently avoided versican positive chondrogenic aggregates. Wild type neural tubes cultured with hdf limb mesenchyme, which does not undergo cartilage differentiation in a wild type pattern, showed that axons exhibited no avoidance characteristics within the host culture. Results suggest that differentiating limb cartilages may limit migration of axons thus aiding in the ultimate patterning of peripheral nerve in the developing limb.

show abstract

Section: Resultssupporting

confidence: 86%

Section: Resultssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neural Tissue Co-Culture with Mesenchyme to Investigate Patterningof Peripheral Nerve During Murine Embryonic Limb Development

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our previous study using N1511 chondrogenic cells clearly demonstrated that inhibition of versican expression at an early stage substantially decelerates following chondrocyte differentiation (34). High density micromass culture systems of limb bud obtained from versican-null hdf homozygote embryos demonstrated that versican is necessary for mesenchymal cell aggregation but that these mesenchymal cells undergo chondrocyte differentiation in three-dimensional type I collagen gel culture (33). These results suggest that versican interacts with other ECM molecules and cell membrane molecules and mechanically ties up individual cells to form aggregates.…”

Section: Discussionmentioning

confidence: 98%

“…These characteristic expression patterns of versican and its effects on cell behavior observed in cell culture systems strongly suggest that versican regulates, in the ECM, the function of ligands that mediate signaling toward cartilage development and synovial joint formation. An in vitro analysis of limb mesenchyme from genetrapped versican-deficient mouse hdf (heart defect) by micromass indicated that versican is necessary for chondrocyte differentiation of mesenchymal cells (33). Our previous studies using N1511 chondrocytic cells demonstrated that versican is required for the mesenchymal matrix formation toward chondrocyte differentiation during chondrogenesis (34).…”

mentioning

confidence: 99%

Versican Facilitates Chondrocyte Differentiation and Regulates Joint Morphogenesis

Choocheep

Hatano

Takagi

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Versican Knock‐Down Compromises Chondrogenesis in the Embryonic Chick Limb

Shepard

Gliga

Morrow

et al. 2007

The Anatomical Record

Self Cite

View full text Add to dashboard Cite

Mesenchymal cell aggregation is critical for cartilage formation in the vertebrate limb. The extracellular matrix (ECM) plays a critical role in governing cell behavior and cell phenotype in this tissue, and the hyalectin versican is highly expressed in the ECM of precartilage mesenchymal cells and developing synovial joints. Although several in vitro studies have been conducted in an attempt to address versican's role during limb mesenchymal condensation, factors such as differences in cell density in culture, variations between chondrogenic cell lines, and the inability to prolong the viability of limb explants have led to conflicting data, mandating an in vivo analysis. By using a morpholino directed strategy in ovo, we performed knock-down of versican expression in the presumptive ulnar region of the developing chick wing at time points critical to skeletogenesis. These data indicate that in ovo misexpression of versican compromised mesenchymal condensation with resulting ulnar cartilages reduced in length distally by an average of 53% relative to contralateral control limbs. In select versican morphants the olecranon process was also reduced in size proximally and failed to cup the humerus, likely impairing joint morphogenesis. This study represents the first report assessing the role of versican in the developing chick limb in ovo, further demonstrating the importance of versican proteoglycan expression during chondrogenesis and extending previous findings to suggest a role for versican during synovial joint development.

show abstract

Limb chondrogenesis is compromised in the versican deficient hdf mouse

Cited by 36 publications

References 35 publications

Neural Tissue Co-Culture with Mesenchyme to Investigate Patterningof Peripheral Nerve During Murine Embryonic Limb Development

Neural Tissue Co-Culture with Mesenchyme to Investigate Patterningof Peripheral Nerve During Murine Embryonic Limb Development

Versican Facilitates Chondrocyte Differentiation and Regulates Joint Morphogenesis

Versican Knock‐Down Compromises Chondrogenesis in the Embryonic Chick Limb

Contact Info

Product

Resources

About