Role of N-cadherin in the sorting-out of mesenchymal cells and in the positional identity along the proximodistal axis of the chick limb bud

Mesenchymal cells from different stages of chick limb buds sort out in mono layer culture, suggesting the presence of different cell affinities depende nt on their positions along the proximodistal axis. However, it is still no t clear which molecules are responsible for the sorting-out. Here, we propo se that N-cadherin, a cell-adhesion molecule, is involved in the sorting-ou t and is likely to be a component of the mechanism of proximodistal pattern ing in the developing limb. N-cadherin proteins accumulate in the distal re gion of the chick limb bud as limb development proceeds. In monolayer cultu re of distal mesenchymal cells, the stage-dependent levels of N-cadherin pr oteins are maintained during cell sorting. The results of this study have a lso demonstrated that an anti-N-cadherin monoclonal antibody, NCD-2, clearl y inhibits the cell sorting. Moreover, removal of the apical ectodermal rid ge or retinoic-acid treatment of distal cells, which results in a change in the pattern of sorting-out, inhibits the accumulation of N-cadherin protei ns, suggesting that the distribution of these proteins is related to the po sitional identity that gives rise to the different shape and number of cart ilage elements along the proximodistal axis. Dev Dyn 1999;216:274-284. (C) 1999 Wiley-Liss, Inc.