Expression of Id2 in the developing limb is associated with zones of active BMP signaling and marks the regions of growth and differentiation of the developing digits.

Here we report the pattern of expression of inhibitor of DNA binding/differentiation factor 2 (Id2) in the developing chicken limb. We show that prior to stage 25, Id2 is expressed in the anterior and posterior mesoderm, the AER, and in the early skeletal chondrogenic aggregates. At more advanced stages of limb development Id2 is expressed in the undifferentiated subectodermal and interdigital mesenchyme and exhibits specific domains of expression in the growing digits. These expression domains were closely coincident with zones of activation of BMP-signaling as deduced from the distribution of phosphorylated SMADs 1/5/8. In micromass cultures transcripts of Id2 are associated with the nodules of chondrogenic differentiation. Expression of Id2 both in vivo and in vitro was up-regulated in experiments of BMP-gain-of-function and down-regulated after treatments with BMP-antagonists. Interestingly, interdigital application of TGFbeta2 transiently upregulates Id2 in coincidence with the inhibition of interdigital cell death and the commitment of the interdigital mesenchyme to form an ectopic digit. These data suggest that Id2 is a molecular mediator of BMP signaling acting in concert with the TGFbeta pathway during the formation of the digits.