Studying enhancer function using the Tbx4 locus as a model

Key developmental processes in embryogenesis are modulated by transcription factors and signaling molecules whose spatio-temporal expression patterns need to be tightly regulated by cis-regulatory elements or enhancers. I first set out to investigate enhancer redundancy in mice using the Tbx4 locus. I show that the two hindlimb specific regulatory elements of Tbx4, HLEA and HLEB, although have overlapping expression patterns in this tissue, do serve distinct roles and are therefore not redundant. Further investigation of the active appendage regulome has uncovered a large overlap between enhancers active in limbs and those active in the genital tubercle. One of these regulatory elements is HLEB which, besides gene expression in the hindlimbs, also drives robust expression in the genital tubercle. I show that this enhancer is not only active in two distinct appendage types, but also is functionally important for the proper development of both tissues.