Self renewal is integral to the creation and maintenance of many tissues and organs including human epithelia, muscle and blood systems. Each of these tissues establishes populations of self-renewing (stem) cells and must ensure that these stem cells divide and create new differentiated cells at the appropriate rate and in the appropriate place;not enough cells or divisions and the tissue will deteriorate, too many divisions and tumors can form. Our long term goal is to understand the mechanism(s) by which dispersed self-renewing populations are established and how their division and differentiation is influenced by interaction with neighboring cells. A powerful set of genetic, molecular and functional genomic tools, combined with the ability to visualize and track cell divisions makes Arabidopsis stomatal development an attractive system for investigating this set of questions. In our previous work we found that a trio of bHLH transcription factors and components of a MAPK pathway modulate division vs. differentiation choices at discrete stages in stomatal development. Based on data from genetic, biochemical and functional assays, we propose that activity of the earliest-acting bHLH in this trio, SPEECHLESS (SPCH), controls the asymmetric divisions that create the self-renewing populations. We show that SPCH is a direct target of MAP kinase-dependent phosphorylation in vitro, and that phosphorylation alters the behavior of SPCH in vivo.
Our specific aims i n this proposal are to: (1) elucidate the molecular mechanisms by which SPCH activity is regulated (2) Create a molecular profile of stomatal lineage cells and identify and functionally characterize transcriptional targets of SPCH in these cells, and (3) Take advantage of SPCH-induced phenotypes to genetically dissect the endogenous signaling network required to repress stem-cell differentiation. Because both the bHLH class of transcriptional regulators and the MAPK pathway are universally conserved, these studies may contribute not only to an understanding of self-renewal, but will contribute to our understanding of the diversity of MAPK and bHLH signaling mechanisms and responses.

Public Health Relevance

Adult stem cells are called upon to regenerate or repair tissues following injury or disease. However, excess division of those same stems can lead to cancer. The proposed studies will thus help to inform strategies to induce stem cells to differentiate into specific tissues while restricting the potential for cancerous overgrowth.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Arts and Sciences
United States
Zip Code
Vatén, Anne; Soyars, Cara L; Tarr, Paul T et al. (2018) Modulation of Asymmetric Division Diversity through Cytokinin and SPEECHLESS Regulatory Interactions in the Arabidopsis Stomatal Lineage. Dev Cell 47:53-66.e5
Lau, On Sun; Song, Zhuojun; Zhou, Zimin et al. (2018) Direct Control of SPEECHLESS by PIF4 in the High-Temperature Response of Stomatal Development. Curr Biol 28:1273-1280.e3
Chater, Caspar C; Caine, Robert S; Tomek, Marta et al. (2016) Origin and function of stomata in the moss Physcomitrella patens. Nat Plants 2:16179
Gu, Fangwei; Bringmann, Martin; Combs, Jonathon R et al. (2016) Arabidopsis CSLD5 Functions in Cell Plate Formation in a Cell Cycle-Dependent Manner. Plant Cell 28:1722-37
Adrian, Jessika; Chang, Jessica; Ballenger, Catherine E et al. (2015) Transcriptome dynamics of the stomatal lineage: birth, amplification, and termination of a self-renewing population. Dev Cell 33:107-18
Lau, On Sun; Bergmann, Dominique C (2015) MOBE-ChIP: a large-scale chromatin immunoprecipitation assay for cell type-specific studies. Plant J 84:443-50
Matos, Juliana L; Lau, On Sun; Hachez, Charles et al. (2014) Irreversible fate commitment in the Arabidopsis stomatal lineage requires a FAMA and RETINOBLASTOMA-RELATED module. Elife 3:
Davies, Kelli A; Bergmann, Dominique C (2014) Functional specialization of stomatal bHLHs through modification of DNA-binding and phosphoregulation potential. Proc Natl Acad Sci U S A 111:15585-90
Lau, On Sun; Davies, Kelli A; Chang, Jessica et al. (2014) Direct roles of SPEECHLESS in the specification of stomatal self-renewing cells. Science 345:1605-9
Kumari, Archana; Jewaria, Pawan K; Bergmann, Dominique C et al. (2014) Arabidopsis reduces growth under osmotic stress by decreasing SPEECHLESS protein. Plant Cell Physiol 55:2037-46

Showing the most recent 10 out of 20 publications