Matrix disruption causes digit fusion (arrow at bottom).

Late in the formation of limbs, rays of condensing tissue appear at the tips of the developing limbs, and then grow and differentiate into digits, while the tissue in between undergoes programmed cell death. Gradients of bone morphogenetic proteins (BMPs) regulate this process, but now Arteaga-Solis et al. (page 275) show that an organized extracellular matrix, generally thought to be restricted to a structural, supportive role, is also necessary for proper limb patterning. In the study, the authors report what happens when mice lack fibrillin 2 (Fbn2), one of the major constituents of the extracellular microfibrils.

Without Fbn2, the three middle digits of the limbs tend to fuse. Thus, the insoluble matrix surrounding cells appears to be necessary for the proper activity of morphogens. The authors speculate that the microfibrillar network may control the distribution of signals in the developing limb or otherwise direct signaling.

The authors also observe a genetic interaction between Fbn2 and BMP7, supporting the idea that fibrillins and morphogens work together. Mice with reduced levels of both proteins show a phenotype that is the sum of the phenotypes in mice that lack either protein entirely. ▪