scholarly journals PAR-1 promotes primary neurogenesis and asymmetric cell divisions via control of spindle orientation

Development ◽  
2010 ◽  
Vol 137 (15) ◽  
pp. 2501-2505 ◽  
Author(s):  
J. M. Tabler ◽  
H. Yamanaka ◽  
J. B. A. Green
eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Angel Morrow ◽  
Julie Underwood ◽  
Lindsey Seldin ◽  
Taylor Hinnant ◽  
Terry Lechler

Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.


2013 ◽  
Vol 368 (1629) ◽  
pp. 20130016 ◽  
Author(s):  
Anita Kulukian ◽  
Elaine Fuchs

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.


2019 ◽  
Author(s):  
Angel Morrow ◽  
Julie Underwood ◽  
Lindsey Seldin ◽  
Taylor Hinnant ◽  
Terry Lechler

SummaryTissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.


Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1035-1047 ◽  
Author(s):  
M.A. Herman ◽  
H.R. Horvitz

The generation and orientation of cellular and organismic polarity are fundamental aspects of development. Mutations in the gene lin-44 of the nematode Caenorhabditis elegans reverse both the relative positions of specific sister cells and the apparent polarities of these cells. Thus, lin-44 mutants appear to generate polar cells but to misorient these cells along the body axis of the animal. We postulate that lin-44 acts to specify the orientation of polar cells.


Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4623-4633 ◽  
Author(s):  
K. Gallagher ◽  
L.G. Smith

In plant cells, cytokinesis depends on a cytoskeletal structure called a phragmoplast, which directs the formation of a new cell wall between daughter nuclei after mitosis. The orientation of cell division depends on guidance of the phragmoplast during cytokinesis to a cortical site marked throughout prophase by another cytoskeletal structure called a preprophase band. Asymmetrically dividing cells become polarized and form asymmetric preprophase bands prior to mitosis; phragmoplasts are subsequently guided to these asymmetric cortical sites to form daughter cells of different shapes and/or sizes. Here we describe two new recessive mutations, discordia1 (dcd1) and discordia2 (dcd2), which disrupt the spatial regulation of cytokinesis during asymmetric cell divisions. Both mutations disrupt four classes of asymmetric cell divisions during the development of the maize leaf epidermis, without affecting the symmetric divisions through which most epidermal cells arise. The effects of dcd mutations on asymmetric cell division can be mimicked by cytochalasin D treatment, and divisions affected by dcd1 are hypersensitive to the effects of cytochalasin D. Analysis of actin and microtubule organization in these mutants showed no effect of either mutation on cell polarity, or on formation and localization of preprophase bands and spindles. In mutant cells, phragmoplasts in asymmetrically dividing cells are structurally normal and are initiated in the correct location, but often fail to move to the position formerly occupied by the preprophase band. We propose that dcd mutations disrupt an actin-dependent process necessary for the guidance of phragmoplasts during cytokinesis in asymmetrically dividing cells.


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