ABSTRACT Developmental transitions are often depicted as highly buffered processes that lead from one stereotypical state to a different stereotypical state. Changes in the relative timing of different processes can have profound consequences for the viability of an organism and, on a longer time scale, for the evolution of a species. The juvenile-to-adult transition in plants (vegetative phase change) is an ideal system in which to study the mechanism and consequences of such heterochronic variation. Compared to other developmental transitions in plants, vegetative phase change is unusual in that it occurs relatively slowly and involves species-specific traits that change gradually from leaf-to-leaf at slightly different rates. As a result, novel combinations of traits are the rule, rather than the exception. This process is controlled by two closely-related miRNAs, miR156 and miR157. miR156/157 are expressed at high levels early in shoot development, but then decline dramatically, relieving the repression of their targets, SPL transcription factors. We hypothesize the plasticity of vegetative phase change is attributable to 1) the functional differentiation of SPL genes; 2) the differential sensitivity of these genes to miR156/157 and 3) natural variation in the level and/or expression pattern of miR156/miR157. We will test this hypothesis in Arabidopsis thaliana by (Aim 1) characterizing the effect of loss- of-function mutations in 6 key SPL genes on gene expression and leaf morphology. The sensitivity of these genes to variation in the level of miR156/miR157 will be examined using transgenic lines containing miR156-sensitive reporters. In Aim 2, we will characterize natural variation in the expression pattern of miR156 and use QTL mapping to identify the genes responsible for this variation. In Aim 3, we will perform a sensitized genetic screen to identify mutations that increase the abundance of miR156 or interfere with its down-regulation, and will determine the molecular identity of these mutations by whole genome sequencing of mutants in segregating populations. In addition to contributing to an understanding of the molecular mechanism and biological functions of vegetative phase change, these experiments address the more general question of whether miRNA-mediated regulation of gene expression facilitates developmental plasticity.