Elsevier

Developmental Biology

Volume 192, Issue 2, 15 December 1997, Pages 492-508
Developmental Biology

Regular Article
Cyr61, Product of a Growth Factor-Inducible Immediate-Early Gene, Regulates Chondrogenesis in Mouse Limb Bud Mesenchymal Cells

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Abstract

Chondrogenesis during embryonic skeletal development involves the condensation of mesenchymal cells followed by their differentiation into chondrocytes. We describe herein a previously unrecognized regulator of mammalian chondrogenesis encoded by a murine growth factor-inducible immediate-early gene,cyr61.The Cyr61 protein is a secreted, heparin-binding protein (379 amino acids with 38 conserved cysteines) that promotes cell adhesion, migration, and proliferation. The expression pattern of thecyr61gene during embryogenesis is tissue specific and temporally regulated. Most notably,cyr61is transiently expressed in mesenchymal cells of both mesodermal and neuroectodermal origins undergoing chondrogenesis, suggesting that Cyr61 may play a role in the development of the embryonic skeleton. In this communication, we demonstrate that the Cyr61 protein promotes chondrogenesis in micromass cultures of limb bud mesenchymal cellsin vitroand is likely to play a similar rolein vivobased on the following observations: (1) Cyr61 is present in the embryonic limb mesenchyme during chondrogenesisin vivoandin vitro;(2) purified recombinant Cyr61 protein added exogenously to micromass cultures promotes chondrogenesis as judged by precocious expression of type II collagen, increased [35S]sulfate incorporation, and larger Alcian blue-staining cartilage nodules; (3) Cyr61 enhances cell–cell aggregation, an initial step in chondrogenesis, and promotes chondrogenic differentiation in cultures plated at subthreshold cell densities that are otherwise unable to support differentiation; and (4) neutralization of the endogenous Cyr61 with specific antibodies inhibits chondrogenesis. Taken together, these results identify Cyr61 as a novel player in chondrogenesis that contributes to the development of the mammalian embryonic skeleton.

Keywords

micromass culture
mouse embryo
connective tissue growth factor
Nov
type II collagen

Cited by (0)

B. K. Hall, Ed.

1

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