Wheat production is currently not keeping up with the demands of an increasing population against the backdrop of a changing climate. To increase yields while overcoming the persistent trade-off between grain number and grain weight, we need to improve our understanding of wheat inflorescence (spike) development. The MADS-box transcription factor (TF) VEGETATIVE TO REPRODUCTIVE TRANSITION A2 (VRT-A2) and the AP2/ERF TF APETALA2-5A (AP2-5A, also known as Q) have important functions in wheat spike development. Both TFs influence agronomically important traits such as plant height, flowering time, and spikelet density, raising the prospect of potential interactions between VRT-A2 and AP2-5A. To test this hypothesis, we crossed ap2-5A knockout mutants to a VRTA2b allele NIL and analyzed the progeny. Consistent with the literature, the ap2-5A single mutants presented an extra pair of bracts (sometimes referred to as empty lemmas) at the base of each spikelet (Debernardi et al., 2017). The single VRT-A2b NIL, which ectopically expresses VRT-A2, developed long glumes and grains (Adamski et al., 2021). Interestingly, ap25A VRT-A2b double mutant spikelets consisted almost entirely of bracts and some florets contained double ovaries. Neither of these phenotypes were observed in the single mutants, strongly suggesting an interaction between VRT-A2 and AP2-5A. Similar phenotypes in the apetala2-2 (ap2-2) ap2-5 double mutant indicate a possible interaction between VRT-A2 and multiple AP2-like genes, not just AP2-5A (Debernardi et al., 2020). We plan to test this interaction using transgenic lines and ChIP-seq to elucidate any protein-DNA binding. The relationship will be characterized in detail by analyzing the expression of VRT-A2, AP2-5A, and AP2-2 in our mutant lines during early spike development using qRT-PCR and in situ hybridization. We will also investigate whether this putative regulatory relationship requires or is dependent on miR172, which is a known regulator of AP2-like genes. Together, these results will shed more light onto the complex interaction between TFs and how they shape plant development.