Linking Cell Cycle to Asymmetric Division: Aurora-A Phosphorylates the Par Complex to Regulate Numb Localization

Wirtz-Peitz, Frederik; Nishimura, Takashi; Knoblich, Juergen A.

doi:10.1016/j.cell.2008.07.049

Cited by 346 publications

(452 citation statements)

References 41 publications

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“…Examples include the distribution of inhibitors of self-renewal, such as Brat and Mei-P26, to daughter cells destined to become TACs in the Drosophila CNS and ovaries, respectively [19,20], and the similar destination of Numb, an inhibitor of Notch signalling, that has a conserved role of controlling lineage specification in a variety of cell types [21]. The relationship between these two intrinsic mechanisms is becoming clearer [22]; in the Drosophila CNS, Aurora A phosphorylates Par6, a regulatory subunit of aPKC that becomes activated and phosphorylates Lethal (2) giant larvae (Lgl), an interphase inhibitor of aPKC. Phosphorylated Lgl is released from aPKC, allowing Baz to join the complex.…”

Section: Self-renewal and The Stem Cell Nichementioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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Section: Self-renewal and The Stem Cell Nichementioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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“…Adult or larval brains were dissected in PBS and fixed for 10 min in 3.7% (vol/vol) formaldehyde in PBS containing 0.2% TritonX-100 and processed as previously described (36). The following primary antibodies were used: mouse anti-Dac, mouse anti-Ey (Developmental Studies Hybridoma Bank), and chick anti-GFP (Abcam).…”

Section: Methodsmentioning

confidence: 99%

Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression

Okamoto¹,

Nishimori²,

Nishimura³

2012

Proc. Natl. Acad. Sci. U.S.A.

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Members of the insulin family peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. The Drosophila genome encodes seven insulin-like peptide genes, dilp1-7, and the most prominent dilps (dilp2, dilp3, and dilp5) are expressed in brain neurosecretory cells known as "insulin-producing cells" (IPCs). Although these dilps are expressed in the same cells, the expression of each dilp is regulated independently. However, the molecular mechanisms that regulate the expression of individual dilps in the IPCs remain largely unknown. Here, we show that Dachshund (Dac), which is a highly conserved nuclear protein, is a critical transcription factor that specifically regulates dilp5 expression. Dac was strongly expressed in IPCs throughout development. dac loss-of-function analyses revealed a severely reduced dilp5 expression level in young larvae. Dac interacted physically with the Drosophila Pax6 homolog Eyeless (Ey), and these proteins synergistically promoted dilp5 expression. In addition, the mammalian homolog of Dac, Dach1/2, facilitated the promoting action of Pax6 on the expression of islet hormone genes in cultured mammalian cells. These observations indicate the conserved role of Dac/Dach in controlling insulin expression in conjunction with Ey/Pax6.

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“…The D. melanogaster neuroblast is a unipotent stem cell that forms a neuroblast cell and a ganglion mother cell, which differentiates into a neuron. The asymmetric division of the neuroblast is conditioned by two cell cycle regulators, Aurora-A and Polo kinase, that phosphorylate a set of polarity-determining proteins and thereby dictate their localization (Wang et al, 2007;Wirtz-Peitz et al., 2008). Similarly, chloronema apical cells in P. patens are polarized, with tip growth at one end, as well as polarized localization of chloroplasts and vacuoles (Menand et al, 2007a;Perroud and Quatrano, 2008).…”

Section: Cdka;1 Links Cell Cycle Progression With Other Cellular Chanmentioning

confidence: 99%

PhyscomitrellaCyclin-Dependent Kinase A Links Cell Cycle Reactivation to Other Cellular Changes during Reprogramming of Leaf Cells

et al. 2011

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During regeneration, differentiated plant cells can be reprogrammed to produce stem cells, a process that requires coordination of cell cycle reactivation with acquisition of other cellular characteristics. However, the factors that coordinate the two functions during reprogramming have not been determined. Here, we report a link between cell cycle reactivation and the acquisition of new cell-type characteristics through the activity of cyclin-dependent kinase A (CDKA) during reprogramming in the moss Physcomitrella patens. Excised gametophore leaf cells of P. patens are readily reprogrammed, initiate tip growth, and form chloronema apical cells with stem cell characteristics at their first cell division. We found that leaf cells facing the cut undergo CDK activation along with induction of a D-type cyclin, tip growth, and transcriptional activation of protonema-specific genes. A DNA synthesis inhibitor, aphidicolin, inhibited cell cycle progression but prevented neither tip growth nor protonemal gene expression, indicating that cell cycle progression is not required for acquisition of protonema cell-type characteristics. By contrast, treatment with a CDK inhibitor or induction of dominant-negative CDKA;1 protein inhibited not only cell cycle progression but also tip growth and protonemal gene expression. These findings indicate that cell cycle progression is coordinated with other cellular changes by the concomitant regulation through CDKA;1.

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Linking Cell Cycle to Asymmetric Division: Aurora-A Phosphorylates the Par Complex to Regulate Numb Localization

Cited by 346 publications

References 41 publications

Attributes of adult stem cells

Attributes of adult stem cells

Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression

PhyscomitrellaCyclin-Dependent Kinase A Links Cell Cycle Reactivation to Other Cellular Changes during Reprogramming of Leaf Cells

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