ABSTRACTA better understanding of spike development can contribute to improving wheat productivity. MADS-box genesVRN1andFUL2(SQUAMOSA-clade) play critical and redundant roles in wheat spike and spikelet development, where they act as repressors of MADS-box genes of theSHORT VEGETATIVE PHASE(SVP) clade (VRT2,SVP1andSVP3). Here, we show that wheatvrt2 svp1mutants are late flowering, have shorter stems, increased number of spikelets per spike and unusual axillary inflorescences in nodes of the elongating stem. Constitutive expression ofVRT2resulted in leafy glumes and lemmas, reversion of basal spikelets to spikes, and down-regulation of MADS-genes involved in floral development. Moreover, constitutive expression ofVRT2enhanced spikelet defects offul2, whereasvrt2reduced vegetative characteristics in the spikelets ofvrn1 ful2mutants heterozygous forVRN-A1. TheseSVP-SQUAMOSAgenetic interactions were paralleled by physical interactions among their encoded proteins. SVP proteins were able to reduce SQUAMOSA-SEPALLATA interactions in yeast-three-hybrid experiments. We propose that SQUAMOSA-SVP complexes act during the early reproductive phase to promote heading, formation of the terminal spikelet, and stem elongation, but that down-regulation ofSVPgenes is then necessary for the formation of SQUAMOSA-SEPALLATA complexes that are required for normal spikelet and floral development.