Generating diverse progenies from a limited number of progenitor cells is a significant challenge for multicellular organisms. The progenitor cells continuously renew themselves while generating new cell types; this process requires asymmetric cell divisions (ACD), a hallmark of stem cells. A key process during ACD is the cellular polarization of progenitor cells. The long-term goal of the research is to elucidate the design principles that govern cellular polarization and cell fate differentiation in plant ACD. The formation and patterning of stomata in plants require precisely controlled ACDs. The Arabidopsis stomata system provides an excellent platform to study the mechanisms for ACD in plants, because these divisions are stereotypic and highly predictable, and the leaf epidermis exposed in the air is readily accessible to genetic characterization and cellular examination. The PI identified the first intrinsic polarity protein in Arabidopsis, BASL (Break Asymmetry of the Stomatal Lineages), that controls ACD by its highly polarized distribution at the plasma membrane. However, how the cortical BASL polarity domain is defined and how cell polarity regulates stomatal ACD remain largely elusive. The proposed studies will apply a comprehensive approach combining genetics, biochemistry, advanced cell biology, and proteomic/phosphoproteomic methods to (1) understand how vesicular trafficking controls targeted membrane delivery to promote the polarization of stomatal ACD cells and (2) determine how polarity-driven, asymmetrically distributed endosomal activity differentiates two daughter cells in plant ACD. The molecular mechanisms under investigation involve protein polarization, endomembrane trafficking, phospholipid signaling, and crosstalk between signal transduction and endosomal function in cell polarization and asymmetric cell division, all of which are clearly related to the studies of human stem cell activity and function.
PROJECTIVE NARRATIVE ! ! Asymmetric cell division (ACD) generates diverse cell types and is universally required for development and patterning in multicellular organisms. One fundamental mechanism that regulates ACD is through cell polarization, the asymmetric distribution of molecules, structures and functions within a cell. The molecular mechanisms by which asymmetric divisions are regulated by cell polarity in plants remain large unknown. By using the Arabidopsis stomata system, which is highly amenable to genetic analysis and cell biological examination, this project focuses on establishing the molecular and cellular paradigms that coordinate cell polarization and asymmetric fate determination during asymmetric divisions, the processes clearly linked to human stem cell activities.! !
