miRNAs as Mobile Signals in Development

Marja Timmermans

Timmermans copy
  • PhD studies at Rutgers University, 1990-1996
  • Postdoctoral training at Yale University, 1996-1998
  • Assistant, Associate, and Full Professor at Cold Spring Harbor Laboratory, 1998-2015
  • Alexander von Humboldt Professor at the University of Tuebingen since 2015

Research Interest

The formation of stable, precisely defined boundaries between two distinct cell fates is a fundamental feature of plant and animal development. Such cell fate boundaries coordinate the differentiation and growth of the tissue or organ. In this regard, development of flat leaf architecture poses an unusual and mechanistically challenging problem; namely, how to create a stable dorsoventral (top-bottom) boundary within the plane of a long and wide, but shallow, structure? We have shown that the positional information needed is provided by mobile small RNAs that reminiscent to classical morphogens generate sharply defined domains of target gene expression through an intrinsic, threshold-based readout of their mobility gradients (Skopelitis et al., 2017).

Major questions regarding the properties and function of mobile small RNAs in development, however, remain: how do small RNAs move, how is their mobility regulated, what are the distinguishing patterning properties of mobile small RNAs, and how might opposing signal gradients interact to achieve the remarkable precision and robustness of developmental programs? We combine classical genetics with single cell genomic approaches, quantitative time-lapse imaging and theoretical modelling to address these questions in the model plant Arabidopsis. Please see here for more detail.

  • Timmermans Fig 1
    click to enlarge

Figure 1. Gradients of mobile small RNAs have morphogen-like patterning activities. Mobility of miRNAs from their site of biogenesis in the bottom epidermis (A) yields a miRNA gradient (B) that through a threshold-based read-out establishes an on-off pattern of target gene expression (C, D).

  • Timmermans Fig 2
    click to enlarge

Figure 2. Synthetic system to study miRNA mobility. In seedlings expressing fluorescent reporters (A), artificial miRNAs targeting these reporters are expressed in a regulated often tissue-specific manner (B) to arrive at the parameters and mechanisms of miRNA mobility (C).

Available PhD Projects

Project 1: Gating of miRNA mobility in plant stem cell niches.

Selected Reading

1) Skopelitis, D.S., Hill, K., Klesen, S., Marco, C.F., von Born, P., et al. (2018) Gating of miRNA movement at defined cell-cell interfaces governs their impact as positional signals. Nat Commun. 9, 3107.

2) Skopelitis, D.S., Benkovics, A.H., Husbands, A.Y., and Timmermans, M.C.P. (2017) Boundary formation through a direct threshold-based readout of mobile small RNA gradients. Dev Cell 43, 265-273.

3) Denyer, T., Ma, X., Klesen, S., Scacchi, E., Nieselt, K., and Timmermans M.C.P. (2019) Spatiotemporal developmental trajectories in the Arabidopsis root revealed using high-throughput single cell RNA sequencing. Dev Cell 48, 840-852.