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1.
Cai Y  Yu F  Lin S  Chia W  Yang X 《Cell》2003,112(1):51-62
Drosophila neuroblast asymmetric divisions generate two daughters of unequal size and fate. A complex of apically localized molecules mediates basal localization of cell fate determinants and apicobasal orientation of the mitotic spindle, but how daughter cell size is controlled remains unclear. Here we show that mitotic spindle geometry and unequal daughter cell size are controlled by two parallel pathways (Bazooka/DaPKC and Pins/G alpha i) within the apical complex. While the localized activity of either pathway alone is sufficient to mediate the generation of an asymmetric mitotic spindle and unequal size neuroblast daughters, loss of both pathways results in symmetric divisions. In sensory organ precursors, Bazooka/DaPKC and Pins/G alpha i localize to opposite sides of the cortex and function in opposition to generate a symmetric spindle.  相似文献   

2.
Asymmetric cell divisions (ACDs) result in two unequal daughter cells and are a hallmark of stem cells. ACDs can be achieved either by asymmetric partitioning of proteins and organelles or by asymmetric cell fate acquisition due to the microenvironment in which the daughters are placed. Increasing evidence suggests that in the mammalian epidermis, both of these processes occur. During embryonic epidermal development, changes occur in the orientation of the mitotic spindle in relation to the underlying basement membrane. These changes are guided by conserved molecular machinery that is operative in lower eukaryotes and dictates asymmetric partitioning of proteins during cell divisions. That said, the shift in spindle alignment also determines whether a division will be parallel or perpendicular to the basement membrane, and this in turn provides a differential microenvironment for the resulting daughter cells. Here, we review how oriented divisions of progenitors contribute to the development and stratification of the epidermis.  相似文献   

3.
Asymmetric cell divisions occur repeatedly during plant development, but the mechanisms by which daughter cells are directed to adopt different fates are not well understood [1,2]. Previous studies have demonstrated roles for positional information in specification of daughter cell fates following asymmetric divisions in the embryo [3] and root [4]. Unequally inherited cytoplasmic determinants have also been proposed to specify daughter cell fates after some asymmetric cell divisions in plants [1,2,5], but direct evidence is lacking. Here we investigate the requirements for specification of stomatal subsidiary cell fate in the maize leaf by analyzing four mutants disrupting the asymmetric divisions of subsidiary mother cells (SMCs). We show that subsidiary cell fate does not depend on proper localization of the new cell wall during the SMC division, and is not specified by positional information acting on daughter cells after completion of the division. Instead, our data suggest that specification of subsidiary cell fate depends on polarization of SMCs and on inheritance of the appropriate daughter nucleus. We thus provide evidence of a role for unequal inheritance of an intracellular determinant in specification of cell fate after an asymmetric plant cell division.  相似文献   

4.
Eric L. Weiss 《Genetics》2012,192(4):1165-1202
Productive cell proliferation involves efficient and accurate splitting of the dividing cell into two separate entities. This orderly process reflects coordination of diverse cytological events by regulatory systems that drive the cell from mitosis into G1. In the budding yeast Saccharomyces cerevisiae, separation of mother and daughter cells involves coordinated actomyosin ring contraction and septum synthesis, followed by septum destruction. These events occur in precise and rapid sequence once chromosomes are segregated and are linked with spindle organization and mitotic progress by intricate cell cycle control machinery. Additionally, critical parts of the mother/daughter separation process are asymmetric, reflecting a form of fate specification that occurs in every cell division. This chapter describes central events of budding yeast cell separation, as well as the control pathways that integrate them and link them with the cell cycle.  相似文献   

5.
Asymmetric cell division generates two daughter cells of differential gene expression and/or cell shape. Drosophila neuroblasts undergo typical asymmetric divisions with regard to both features; this is achieved by asymmetric segregation of cell fate determinants (such as Prospero) and also by asymmetric spindle formation. The loss of genes involved in these individual asymmetric processes has revealed the roles of each asymmetric feature in neurogenesis, yet little is known about the fate of the neuroblast progeny when asymmetric processes are blocked and the cells divide symmetrically. We genetically created such neuroblasts, and found that in embryos, they were initially mitotic and then gradually differentiated into neurons, frequently forming a clone of cells homogeneous in temporal identity. By contrast, larval neuroblasts with the same genotype continued to proliferate without differentiation. Our results indicate that asymmetric divisions govern lineage length and progeny fate, consequently generating neural diversity, while the progeny fate of symmetrically dividing neuroblasts depends on developmental stages, presumably reflecting differential activities of Prospero in the nucleus.  相似文献   

6.
The ability of dividing cells to produce daughters with different fates is an important developmental mechanism conserved from bacteria to fungi, plants, and metazoan animals. Asymmetric outcomes of a cell division can be specified by two general mechanisms: asymmetric segregation of intrinsic fate determinants or asymmetric placement of daughter cells into microenvironments that provide extrinsic signals that direct cells to different states. For both, spindle orientation must be coordinated with the localization of intrinsic determinants or source of extrinsic signals to achieve the proper asymmetric outcome. Recent work on spindle orientation in Drosophila melanogaster male germline stem cells and neuroblasts has brought into sharp focus the key role of differential centrosome behavior in developmentally programmed asymmetric division (for reviews see Cabernard, C., and C.Q. Doe. 2007. Curr. Biol. 17:R465-R467; Gonzalez, C. 2007. Nat. Rev. Genet. 8:462-472). These findings provide new insights and suggest intriguing new models for how cells coordinate spindle orientation with their cellular microenvironment to regulate and direct cell fate decisions within tissues.  相似文献   

7.
Asymmetric cell divisions produce two sibling cells with distinct fates, providing an important means of generating cell diversity in developing embryos. Many examples of such cell divisions have been described, but so far only a limited number of the underlying mechanisms have been elucidated. Here, we have uncovered a novel mechanism controlling an asymmetric cell division in the ascidian embryo. This division produces one notochord and one neural precursor. Differential activation of extracellular-signal-regulated kinase (ERK) between the sibling cells determines their distinct fates, with ERK activation promoting notochord fate. We first demonstrate that the segregation of notochord and neural fates is an autonomous property of the mother cell and that the mother cell acquires this functional polarity via interactions with neighbouring ectoderm precursors. We show that these cellular interactions are mediated by the ephrin-Eph signalling system, previously implicated in controlling cell movement and adhesion. Disruption of contacts with the signalling cells or inhibition of the ephrin-Eph signal results in the symmetric division of the mother cell, generating two notochord precursors. Finally, we demonstrate that the ephrin-Eph signal acts via attenuation of ERK activation in the neural-fated daughter cell. We propose a model whereby directional ephrin-Eph signals functionally polarise the notochord/neural mother cell, leading to asymmetric modulation of the FGF-Ras-ERK pathway between the daughter cells and, thus, to their differential fate specification.  相似文献   

8.
Asymmetric segregation of cell-fate determinants during cell division plays an important part in generating cell diversity in invertebrates. We showed previously that cells in the neonatal rat retina divide at various orientations and that some dividing cells asymmetrically distribute the cell-fate determinant Numb to the two daughter cells. Here, we test the possibility that such asymmetric divisions contribute to retinal cell diversification. We have used long-term videomicroscopy of green-fluorescent-protein (GFP)-labeled retinal explants from neonatal rats to visualize the plane of cell division and follow the differentiation of the daughter cells. We found that cells that divided with a horizontal mitotic spindle, where both daughter cells should inherit Numb, tended to produce daughters that became the same cell type, whereas cells that divided with a vertical mitotic spindle, where only one daughter cell should inherit Numb, tended to produce daughters that became different. Moreover, overexpression of Numb in the dividing cells promoted the development of photoreceptor cells at the expense of interneurons and Müller glial cells. These findings indicate that the plane of cell division influences cell-fate choice in the neonatal rat retina and support the hypothesis that the asymmetric segregation of Numb normally influences some of these choices.  相似文献   

9.
Asymmetric cell divisions in which a precursor cell distributes fate potential unequally between the two daughter cells represent one of the major mechanisms for fate specification during development. Such mechanisms suggest at least two distinct cellular activities: factors that act to establish asymmetry in the precursor cell and factors that are distributed or activated unequally and function to make the daughter cells different from each other. In Caenorhabditis elegans , cytokinesis of the first division of the male-specific postembryonic blast cell B is unequal, and the two daughters adopt different fates. Others have observed that the genes lin-17 and lin-44 are required, respectively, to establish and to orient this asymmetric division. Mutations in lin-17 and lin-44 coordinately disrupt cytokinesis and fate specification. We describe the function of the gene vab-3 in the B cell lineage. Mutations in vab-3 disrupt the fate of the anterior daughter of B, B.a. However, unlike lin-17 and lin-44 , mutations in vab-3 can disrupt fate without the corresponding disruption of unequal cytokinesis. Analysis of lin-17; vab-3 double mutants suggests that vab-3 acts after lin-17 for B.a fate specification. Double mutant analysis has also identified additional functions of lin-17 in the B lineage subsequent to this first division.  相似文献   

10.
Sun Y  Goderie SK  Temple S 《Neuron》2005,45(6):873-886
It has been debated whether asymmetric distribution of cell surface receptors during mitosis could generate asymmetric cell divisions by yielding daughters with different environmental responsiveness and, thus, different fates. We have found that in mouse embryonic forebrain ventricular and subventricular zones, the EGFR can distribute asymmetrically during mitosis in vivo and in vitro. This occurs during divisions yielding two Nestin+ progenitor cells, via an actin-dependent mechanism. The resulting sibling progenitor cells respond differently to EGFR ligand in terms of migration and proliferation. Moreover, they express different phenotypic markers: the EGFRhigh daughter usually has radial glial/astrocytic markers, while its EGFRlow sister lacks them, indicating fate divergence. Lineage trees of cultured cortical glioblasts reveal repeated EGFR asymmetric distribution, and asymmetric divisions underlie formation of oligodendrocytes and astrocytes in clones. These data suggest that asymmetric EGFR distribution contributes to forebrain development by creating progenitors with different proliferative, migratory, and differentiation responses to ligand.  相似文献   

11.
Stomata are specialized epidermal structures that regulate gas (CO(2) and O(2)) and water vapor exchange between plants and their environment. In Arabidopsis thaliana, stomatal development is preceded by asymmetric cell divisions, and stomatal distribution follows the one-cell spacing rule, reflecting the coordination of cell fate specification. Stomatal development and patterning are regulated by both genetic and environmental signals. Here, we report that Arabidopsis MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6, two environmentally responsive mitogen-activated protein kinases (MAPKs), and their upstream MAPK kinases, MKK4 and MKK5, are key regulators of stomatal development and patterning. Loss of function of MKK4/MKK5 or MPK3/MPK6 disrupts the coordinated cell fate specification of stomata versus pavement cells, resulting in the formation of clustered stomata. Conversely, activation of MKK4/MKK5-MPK3/MPK6 causes the suppression of asymmetric cell divisions and stomatal cell fate specification, resulting in a lack of stomatal differentiation. We further establish that the MKK4/MKK5-MPK3/MPK6 module is downstream of YODA, a MAPKKK. The establishment of a complete MAPK signaling cascade as a key regulator of stomatal development and patterning advances our understanding of the regulatory mechanisms of intercellular signaling events that coordinate cell fate specification during stomatal development.  相似文献   

12.
During metazoan development, cell fate diversity is generated in part by asymmetric cell divisions, in which mother cells divide to produce two daughter cells with distinct developmental potentials. Adoption of different cell fates often relies on the polarised distribution and unequal segregation of cell-fate determinants. Unequal segregation of cell-fate determinants requires that the mother cell becomes polarised prior to mitosis. In response to this polarisation, cell-fate determinants localise asymmetrically and the mitotic spindle lines up with the pole to which cell-fate determinants accumulate, thereby leading to their unequal partitioning upon cytokinesis. I review here the regulatory mechanisms that establish cell asymmetry and orient this asymmetry relative to the body axis in the sensory organ lineages of Drosophila.  相似文献   

13.
From invertebrates to mammals, cell-cycle progression during an asymmetric cell division is accompanied by precisely timed redistribution of cell-fate determinants so that they segregate asymmetrically to enable the two daughter cells to choose different fates. Interestingly, studies on how cell fates are specified in such divisions reveal that the same fate determinants can be reiteratively used to specify a variety of cell types through multiple rounds of cell divisions or to exert seemingly contradictory effects on cell proliferation and differentiation. Here I summarize the molecular mechanisms governing asymmetric cell division and review recent findings pointing to a novel mechanism for coupling intracellular signaling and cell-cycle progression. This mechanism uses changes in the morphology, subcellular distribution, and molecular composition of cellular organelles like the Golgi apparatus and centrosomes, which not only accompany the progression of cell cycle to activate but also temporally constrain the activity of fate determinants during asymmetric cell divisions.  相似文献   

14.
Asymmetric cell division is a mechanism for achieving cellular diversity. In C. elegans, many asymmetric cell divisions are controlled by the Wnt-MAPK pathway through POP-1/TCF. It is poorly understood, however, how POP-1 determines the specific fates of daughter cells. We found that nob-1/Hox, ceh-20/Pbx, and a Meis-related gene, psa-3, are required for asymmetric division of the T hypodermal cell. psa-3 expression was asymmetric between the T cell daughters, and it was regulated by POP-1 through a POP-1 binding site in the psa-3 gene. psa-3 expression was also regulated by NOB-1 and CEH-20 through a NOB-1 binding sequence in a psa-3 intron. PSA-3 can bind CEH-20 and function after the T cell division to promote the proper fate of the daughter cell. These results indicate that cooperation between Wnt signaling and a Hox protein functions to determine the specific fate of a daughter cell.  相似文献   

15.
Asymmetric cell divisions are central to the generation of cell-fate diversity because factors that are present in a mother cell and distributed unequally at cell division can generate distinct daughters. The process o f asymmetric cell division can be described as consisting of three steps: setting up an asymmetric cue in the mother cell, localizing factors with respect to this cue, and positioning the plane o f cell division so that localized factors are partitioned asymmetrically between daughters. This review describes how specialized cortical domains play a key role in each of these steps and discusses our current understanding of the molecular nature o f cortical domains and the mechanisms by which they may orchestrate asymmetric cell divisions.  相似文献   

16.
Mutations in tcl-2 cause defects in the specification of the fates of the descendants of the TL and TR blast cells, whose polarity is regulated by lin-44/Wnt and lin-17/frizzled, during Caenorhabditis elegans development. In wild-type animals, POP-1/TCF/LEF, is asymmetrically distributed to the T cell daughters, resulting in a higher level of POP-1 in the nucleus of the anterior daughter. The POP-1 asymmetric distribution is controlled by lin-44 and lin-17. However, in tcl-2 mutants, POP-1 is equally distributed to T cell daughters as is observed in lin-17 mutants, indicating that, like lin-17, tcl-2 functions upstream of pop-1. In addition, tcl-2 mutations cause defects in the development of the gonad and the specification of fate of the posterior daughter of the P12 cell, both of which are controlled by the Wnt pathway. Double mutant analyses indicate that tcl-2 can act synergistically with the Wnt pathway to control gonad development as well as P12 descendant cell fate specification. tcl-2 encodes a novel protein. A functional tcl-2::gfp construct was weakly expressed in the nuclei of the T cell and its descendants. Our results suggest that tcl-2 functions with Wnt pathways to control T cell fate specification, gonad development, and P12 cell fate specification.  相似文献   

17.
For the understanding of histogenetic events in the 3-D retinal neuroepithelium, direct observation of the progenitor cells and their morphological changes is required. A slice culture method has been developed by which the behavior of single progenitor cells can be monitored. Although it has been believed that each retinal progenitor cell loses its basal process while it is in M phase, it is reported here that the process is retained throughout M phase and is inherited by one daughter cell, which can be a neuron or a progenitor cell. Daughter neurons used an inherited process for neuronal translocation and positioning. In divisions that produced two mitotic daughters, both of which subsequently divided to form four granddaughter cells, only one daughter cell inherited the original basal process while the other extended a new process. Interestingly, behavioral differences were often noted between such mitotic sisters in the trajectory of interkinetic nuclear movement, cell cycle length, and the composition of the granddaughter pair. Therefore, "symmetric" (progenitor --> progenitor + progenitor) divisions are in fact morphologically asymmetric, and the behavior of the mitotic daughters can often be asymmetric, indicating the necessity for studying possible associations between the process inheritance and the cell fate choice.  相似文献   

18.
不对称细胞分裂是动物发育过程中用以调控细胞分化的一种进化上保守的基本模式。极性的祖细胞通过不对称分裂产生两个不同命运的子细胞,这一过程涉及细胞命运决定因子的不对称分布、纺锤体的旋转定位等,而这些过程都必须依赖特定细胞极性的存在才能得以正常进行。简要综述了高度保守的蛋白复合物PAR/aPKC在细胞极性建立和维持中的重要作用,以及它如何调控纺锤体定位和命运决定因子不对称分配,并讨论了在该领域的一些新发现和研究进展。  相似文献   

19.
The stem cells (SCs) at the bottom of intestinal crypts tightly contact niche-supporting cells and fuel the extraordinary tissue renewal of intestinal epithelia. Their fate is regulated stochastically by populational asymmetry, yet whether asymmetrical fate as a mode of SC division is relevant and whether the SC niche contains committed progenitors of the specialized cell types are under debate. We demonstrate spindle alignments and planar cell polarities, which form a novel functional unit that, in SCs, can yield daughter cell anisotropic movement away from niche-supporting cells. We propose that this contributes to SC homeostasis. Importantly, we demonstrate that some SC divisions are asymmetric with respect to cell fate and provide data suggesting that, in some SCs, mNumb displays asymmetric segregation. Some of these processes were altered in apparently normal crypts and microadenomas of mice carrying germline Apc mutations, shedding new light on the first stages of progression toward colorectal cancer.  相似文献   

20.
《The Journal of cell biology》1994,127(6):1985-1993
The yeast Saccharomyces cerevisiae typically divides asymmetrically to give a large mother cell and a smaller daughter cell. As mother cells become old, they enlarge and produce daughter cells that are larger than daughters derived from young mother cells. We found that occasional daughter cells were indistinguishable in size from their mothers, giving rise to a symmetric division. The frequency of symmetric divisions became greater as mother cells aged and reached a maximum occurrence of 30% in mothers undergoing their last cell division. Symmetric divisions occurred similarly in rad9 and ste12 mutants. Strikingly, daughters from old mothers, whether they arose from symmetric divisions or not, displayed reduced life spans relative to daughters from young mothers. Because daughters from old mothers were larger than daughters from young mothers, we investigated whether an increased size per se shortened life span and found that it did not. These findings are consistent with a model for aging that invokes a senescence substance which accumulates in old mother cells and is inherited by their daughters.  相似文献   

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