Cell polarity and asymmetric division in plants

描述（由申请人提供）：从有限数量的祖细胞产生多样化的后代是多细胞生物的重大挑战。祖细胞需要不断更新自己，同时产生新的细胞类型;这个过程需要不对称细胞分裂（ACD），这是干细胞的标志。ACD的关键过程是祖细胞的细胞极化，这是由外在或内在线索启动的，并最终决定了两个子细胞的差异细胞命运。我们研究的长期目标是阐明ACD中细胞极化和命运决定过程中控制精心安排的事件的设计原则和范式。气孔的形成和图案化需要精确调控的ACD。拟南芥气孔系统提供了一个很好的平台来研究植物ACD的机制，因为这些分裂是刻板的和高度可预测的，并且暴露在空气中的叶表皮很容易获得遗传特征和细胞检查。BASL（Break Asymmetry of the Stomatal Lineages）蛋白是植物中发现的第一个利用气孔系统的优势，通过其高度极化的功能控制ACD的内在极性蛋白。 分布在质膜上。然而，BASL极性如何形成以及它如何调节气孔ACD仍然是一个谜。本申请的中心假设是极性蛋白BASL和保守的MAPK通路之间的新反馈调节在细胞极性建立和不对称细胞命运决定中起重要作用。本研究的三个具体目标是：1）阐明BASL从细胞核到细胞皮层极化的分子机制，2）研究BASL与MAPK通路之间的相互依赖性以及控制质膜上基于BASL的极性的机制，3）建立极性蛋白如何协调植物ACD中子细胞命运的新范式。除了这个核心主题，拟议的全基因组调查BASL物理合作伙伴和新的遗传网络有望提供第一次瞥见的系统控制的内在细胞极性建立在植物ACD。 研究中的分子机制涉及蛋白质亚细胞极化、极性蛋白驱动的细胞命运特化以及MAPK在平衡细胞分裂和分化中的功能，这些都与人类干细胞活性和稳态的研究明确相关。

DESCRIPTION (provided by applicant): Generating diverse progenies from a limited number of progenitor cells is a significant challenge for multicellular organisms. The progenitor cells need to continuously renew themselves while generating new cell types; this process requires asymmetric cell divisions (ACD), a hallmark of stem cells. The key process during ACD is the cellular polarization of progenitor cells, which is initiated by either extrinsic or intrinsic cuesand eventually determines the adoption of differential cell fates in the two daughter cells. The long-term goal of our research is to elucidate the design principles and paradigms that govern the orchestrated events during cellular polarization and fate determination in ACD. The formation and patterning of stomata require precisely regulated 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 air is readily accessible to genetic characterization and cellular examination. Benefited from the advantages of the stomatal system, the novel protein, BASL (Break Asymmetry of the Stomatal Lineages), is the first intrinsic polarity protein identified in plants that controls ACD by its highly polarized distribution at the plasma membrane. However, how BASL polarity is formed and how it regulates stomatal ACD remains elusive. The central hypothesis in this application is that a new feedback regulation between the polarity protein BASL and a conserved MAPK pathway plays an important role in cell polarity establishment and asymmetric cell fate determination. Three specific aims in this proposal are: 1) to elucidate the molecular mechanisms by which BASL is polarized from the nucleus to the cell cortex, 2) to investigate the inter-dependency between BASL and the MAPK pathway and the machineries that control BASL-based polarity at the plasma membrane, and 3) to establish a new paradigm for how polarity proteins coordinate daughter cell fates in plant ACD. Besides this core theme, the proposed genome-wide investigation of BASL physical partners and novel genetic networks promises to provide the first glimpse of the systematic control of intrinsic cell polarity establishment during ACD in plants. The molecular mechanisms under investigation involve protein subcellular polarization, polarity protein- driven cell fate specification, and MAPK functions in balancing cell division and differentiation, which are all clearly linked to the studies of human stem cell activity and homeostasis.