Hox-TALE factors are involved in patterning the vertebrate limb but precisely how they regulate specific and regional gene expression patterns is unclear. Here, on p. , YiPing Chen and co-workers uncover a limb patterning transcriptional programme that is coordinated by the transcription factor Shox2. The researchers demonstrate that, although Shox2 is expressed in mesenchymal progenitors of multiple cell types in the proximal limb, its deletion specifically in the osteogenic lineage causes limb defects and loss of the stylopod – the most proximal region of the limb. ChIP-Seq analyses indicate that Shox2 binds predominantly to limb-specific enhancers that are involved in skeletogenesis; these regions are also co-occupied by Hox-TALE factors. Finally, the authors show that Shox2 is expressed in a gradient that is complementary to that of TALE factors and that it represses the expression of TALE factors in the stylopod. Overall, these observations, together with other findings, highlight the existence of a Shox2-coordinated transcriptional programme that functions to pattern the vertebrate limb and provide insights into the ‘enhancer grammar’ that is used to mediate specific transcriptional outputs.
