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

Multicellular organisms depend on cell-to-cell communication to coordinate development. Recent findings revealed that in addition to peptide ligands, transcription factors, and hormones, plants use small RNAs as positional instructive signals. An obvious advantage of employing mobile small RNAs is that they represent a distinct class of signaling molecules that possess high specificity and whose movement can, in principle, be regulated independently from that of other developmental signals. Moreover, mathematical modeling predicts that mobile small RNAs have the intrinsic property to generate sharply defined on-off boundaries of target gene expression, a prediction for which our preliminary data provide compelling experimental support.

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 quantitative imaging and theoretical approaches to address these questions in model plants, such as Arabidopsis, maize, and moss. This information will be used to understand the interplay of signals that coordinate the many patterning processes occurring in close spatial and temporal vicinity within the developing organism.

  • 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: Stochastic patterning as a bed-hedging strategy in development.

Project 2: Dynamic network properties underlying boundary formation.

Selected Reading

1) Plavskin, Y., Nagashima, A., Perroud, P.-F., Hasebe, M., Quatrano, R.S., Atwal, G.S., and Timmermans M.C.P. (2016) Ancient trans-acting siRNAs confer robustness and sensitivity onto the auxin response. Dev Cell 36, 276-289.

2) Chitwood DH, Nogueira FTS, Howell M, Montgomery TA, Carrington JC, and Timmermans MCP (2009). Pattern formation via small RNA mobility. Genes & Dev. 23: 549-554.

3) Benkovics AH, and Timmermans MCP (2014). Developmental patterning by gradients of mobile small RNAs. Curr Opin Genet Dev. 27: 83-91.