Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

Noatynska, Anna; Tavernier, Nicolas; Gotta, Monica; Pintard, Lionel

doi:10.1098/rsob.130083

Cited by 47 publications

(37 citation statements)

References 122 publications

(197 reference statements)

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“…Although we cannot rule out the possibility that the array data simply reflect the reduction in the proliferating cell population and the corresponding increase of differentiated cells, it might imply a direct link between cell polarity protein function and proliferative capability through E2F family regulation. Intriguingly, the C. elegans E2F gene is implicated in establishing early embryonic polarity, a process in which apical polarity complex proteins play a major role, consistent with a functional connection (Noatynska et al, 2013;Page et al, 2001;Rabilotta et al, 2015;St Johnston and Ahringer, 2010). Our study therefore firmly establishes that Pals1 serves an essential function in the cell cycle progression of cerebellar progenitor cells, possibly by regulating the E2F family transcriptional network.…”

Section: Cerebellar Progenitors Require Pals1 To Remain In the Cyclinmentioning

confidence: 52%

Apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state

et al. 2015

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Through their biased localization and function within the cell, polarity complex proteins are necessary to establish the cellular asymmetry required for tissue organization. Well-characterized germinal zones, mitogenic signals and cell types make the cerebellum an excellent model for addressing the crucial function of polarity complex proteins in the generation and organization of neural tissues. Deletion of the apical polarity complex protein Pals1 in the developing cerebellum results in a remarkably undersized cerebellum with disrupted layers in poorly formed folia and strikingly reduced granule cell production. We demonstrate that Pals1 is not only essential for cerebellum organogenesis, but also for preventing premature differentiation and thus maintaining progenitor pools in cerebellar germinal zones, including cerebellar granule neuron precursors in the external granule layer. In the Pals1 mouse mutants, the expression of genes that regulate the cell cycle was diminished, correlating with the loss of the proliferating cell population of germinal zones. Furthermore, enhanced Shh signaling through activated Smo cannot overcome impaired cerebellar cell generation, arguing for an epistatic role of Pals1 in proliferation capacity. Our study identifies Pals1 as a novel intrinsic factor that regulates the generation of cerebellar cells and Pals1 deficiency as a potential inhibitor of overactive mitogenic signaling.

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Section: Cerebellar Progenitors Require Pals1 To Remain In the Cyclinmentioning

confidence: 52%

Apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state

et al. 2015

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“…Since asymmetric distribution of cell-fate determinants enables two daughter cells to follow different fates, the cell cycle may be linked to cell fate through the establishment of cell polarity, as shown in Caenorhabditis elegans and Drosophila melanogaster (Noatynska et al 2013). Previous work has shown that young LT-HSCs undergo both symmetric and asymmetric division and that the precise balance between the two is affected by various signals (Wu et al 2007).…”

Section: A Cell Cycle-dependent Interplay Between Aging and Differentmentioning

confidence: 99%

Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells

et al. 2015

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Both intrinsic cell state changes and variations in the composition of stem cell populations have been implicated as contributors to aging. We used single-cell RNA-seq to dissect variability in hematopoietic stem cell (HSC) and hematopoietic progenitor cell populations from young and old mice from two strains. We found that cell cycle dominates the variability within each population and that there is a lower frequency of cells in the G1 phase among old compared with young long-term HSCs, suggesting that they traverse through G1 faster. Moreover, transcriptional changes in HSCs during aging are inversely related to those upon HSC differentiation, such that old short-term (ST) HSCs resemble young long-term (LT-HSCs), suggesting that they exist in a less differentiated state. Our results indicate both compositional changes and intrinsic, population-wide changes with age and are consistent with a model where a relationship between cell cycle progression and selfrenewal versus differentiation of HSCs is affected by aging and may contribute to the functional decline of old HSCs.

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“…In animals, polarized cells only divide after polarity is fully established, so that polarized elements are correctly segregated into the daughter cells (Noatynska et al, 2013). In stomatal lineage cells, however, how the cell cycle is coordinated with specific cell polarity factors has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

The chemical compound bubblin induces stomatal mispatterning in Arabidopsis by disrupting the intrinsic polarity of stomatal lineage cells

et al. 2017

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Stem cell polarization is a crucial step in asymmetric cell division, which is a universal system for generating cellular diversity in multicellular organisms. Several conventional genetics studies have attempted to elucidate the mechanisms underlying cell polarization in plants, but it remains largely unknown. In plants, stomata, which are valves for gas exchange, are generated through several rounds of asymmetric divisions. In this study, we identified and characterized a chemical compound that affects stomatal stem cell polarity. Highthroughput screening for bioactive molecules identified a pyridinethiazole derivative, named bubblin, which induced stomatal clustering in Arabidopsis epidermis. Bubblin perturbed stomatal asymmetric division, resulting in the generation of two identical daughter cells. Both cells continued to express the stomatal fate determinant SPEECHLESS, and then differentiated into mispatterned stomata. Bubblin-treated cells had a defect in the polarized localization of BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL), which is required for asymmetric cell fate determination. Our results suggest that bubblin induces stomatal lineage cells to divide without BASL-dependent pre-mitotic establishment of polarity. Bubblin is a potentially valuable tool for investigating cell polarity establishment in stomatal asymmetric division.

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Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

Cited by 47 publications

References 122 publications

Apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state

Apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state

Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells

The chemical compound bubblin induces stomatal mispatterning in Arabidopsis by disrupting the intrinsic polarity of stomatal lineage cells

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