A fascinating question in biology is to understand the processes driving the formation of tissues and organs during embryonic development. The developing limb is a great system to study these processes and we have made major progress in understanding what it takes to make a limb skeleton. For example, our group has identified a basic gene regulatory network (GRN) involved in setting the very early asymmetry of the hand i.e why we have five digits with different identities from thumb to pinky. This GRN is controlled by two transcriptions factors HAND2 and GLI3, which genetically interact to repress each other (Pascal te Welscher et al., 2002, Galli et al., 2010, Osterwalder et al., 2014). While some interactions in this GRN have been shown to be direct, most have been deduced from genetic experiments. I am interested in identifying the transcription factor complexes that set early limb asymmetry and for this I will use a method called rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME, Mohammed et al., 2016). With this method we can perform chromatin immunoprecipitation of given transcription factors and identify the proteins that form a complex with them while they are bound to chromatin. As a given transcription factor can form complexes with different proteins depending on the cell type, one challenge will be to understand the role of interacting partners in the developing limb.