NFATc1 self-promotes to build bone

Self-promotion is the way to get ahead during bone development, according to Asagiri and colleagues. They show on page 1261 that the inducible transcription factor NFATc1 must turn on its own expression for bone-resorbing osteoclasts to form.

NFATc1 drives osteoclast-specific gene expression and is essential for the development of these cells in vitro. But whether NFATc1 is required in vivo was unknown, as deletion of the NFATc1 gene is lethal in mice. Another open questions was whether NFATc2—NFATc1's closest relative—can drive osteoclast formation in the absence of NFATc1.

Asagiri and colleagues now show that NFATc1 is indeed essential for osteoclast formation in vivo, as only NFATc1-expressing stem cells rescued osteoclast development when transferred into osteoclast-deficient mice. NFATc1-deficient stem cells failed at this task, despite having normal expression of NFATc2.

Transcriptional regulation explained why only...