Position-specific growth of mouse limb bud cells in vitro.

The relationship between cellular position and growth control has been studied in cultures of dissociated fragments of mouse limb bud cells. Using cells derived from various positions along the anterior-posterior axis of the limb bud we have developed culture conditions that optimize growth of positionally isolated cells. Under these conditions limb bud cells display an inherent, position-specific growth response; proliferation of cells derived from anterior and central regions of the limb is enhanced over that of posterior derived cells. Thus, within the total population of limb bud cells the in vitro growth of posterior cells is unique and correlates with the positional activity associated with the zone of polarizing activity. Anterior and posterior cells were cocultured to determine whether interactions between these two groups of positionally distinct cells lead to the stimulation of growth that has been observed in vivo. We observe a slight but consistent position-dependent stimulation of growth that is indicative of a mitogenic signal passing between these positionally disparate cells. Similarities between position-related growth dynamics in vivo and in vitro suggest that positional interactions that are important for limb formation can occur between dissociated cells cultured under standard conditions.