RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells

Sedzinski, Jakub; Hannezo, Édouard; Tu, Fan; Biro, Maté; Wallingford, John B.

doi:10.1242/jcs.194704

Cited by 45 publications

(30 citation statements)

References 48 publications

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“…Finally, it is possible that the apical cytoskeleton helps instruct the centriole amplification pathway to regulate centriole abundance per cell. It is well established that an apical actin network in MCC plays a critical role in modulating the surface area, regulating centriole migration and docking at the plasma membrane, ensuring the even distribution of centrioles across the cell surface, and orienting (planar polarization) of centrioles [51][52][53][54][55][56][57][58] . What remains unclear is whether this actin network communicates with the centriole amplification machinery to regulate centriole number.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Cilia Abundance in Multiciliated Cells

Nanjundappa¹,

Kong

Shim³

et al. 2018

Preprint

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Multiciliated cells (MCC) are specialized epithelia that contain hundreds of motile cilia used to propel fluid over the surface of the cell. To template these cilia, each MCC produces hundreds of centrioles by a process termed centriole amplification. Airway progenitor cells initially contain two parental centrioles that nucleate multiple centrioles at once, and structures called deuterosomes that assemble the vast majority of centrioles during amplification. Remarkably, how each cell regulates the precise number of its centrioles and cilia remains unknown. Here, we investigate mechanisms that establish centriole number in MCC using an ex vivo airway culture model. We show that ablation of parental centrioles, via inhibition of Plk4 kinase, does not perturb deuterosome formation and centriole amplification, nor alter the total complement of centrioles per cell. Airway MCC vary in size and surface area, and exhibit a broad range in centriole number. Quantification of centriole abundance in vitro and in vivo identified a direct relationship between cell-surface area and centriole number. By manipulating cell size and shape, we discovered that centriole number scales with increasing surface area. Collectively, our results demonstrate that parental centrioles and Plk4 are dispensable for deuterosome formation, centriole amplification, and establishment of centriole number. Instead, a cell-intrinsic surface area-dependent mechanism controls centriole and cilia abundance in multiciliated cells.

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Section: Discussionmentioning

confidence: 99%

Regulation of Cilia Abundance in Multiciliated Cells

Nanjundappa¹,

Kong

Shim³

et al. 2018

Preprint

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“…Dsp could also have an indirect role in apical expansion, where disruption of Dsp affects actin accumulation. Rho directed apical accumulation of actin has been shown to be critical for apical emergence of intercalating cells (Sedzinski et al, 2016(Sedzinski et al, , 2017. In support of this idea is evidence that desmosome associated plakophilin 2 recruits active RhoA to drive actin reorganization (Godsel et al, 2010).…”

Section: Dsp Is Required For Morphogenesis Of the Epidermis In X Laevismentioning

confidence: 92%

“…PCP signals together with microtubule and associated proteins are important for polarizing and inserting the inner cells into the outer epidermal layer (Kim et al, 2012;Kim et al, 2018;Mitchell et al, 2009;Ossipova et al, 2015;Werner et al, 2014). Finally, apical expansion of the intercalating MCC cell is regulated by RhoA signals combined with formins and actin (Sedzinski et al, 2016(Sedzinski et al, , 2017. Whether desmosomes have a role in radial intercalation of the epidermis has never been explored.…”

Section: Introductionmentioning

confidence: 99%

Desmoplakin is required for epidermal integrity and morphogenesis in theXenopus laevisembryo

Bharathan

Dickinson

2018

Preprint

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Statement: Critical desmosomal protein, desmoplakin, is required for proper distribution and levels of cytoskeletal elements and e-cadherin. Thus embryos with decreased desmoplakin have defects in epidermal integrity and morphogenesis. AbstractDesmoplakin (Dsp) is a unique and critical desmosomal protein, however, it is unclear whether this protein and desmosomes themselves are required for epidermal morphogenesis. Using morpholinos or Crispr/Cas9 mutagenesis we decreased the function of Dsp in frog embryos to better understand its role during epidermal development. Dsp morphant and mutant embryos had developmental defects that mimicked what has been reported in mammals. Such defects included epidermal fragility which correlated with reduction in cortical keratin and junctional e-cadherin in the developing epidermis. Dsp protein sequence and expression are also highly similar with mammals and suggest shared function across vertebrates. Most importantly, we also uncovered a novel function for Dsp in the morphogenesis of the epidermis in X. laevis. Specifically, Dsp is required during the process of radial intercalation where basally located cells move into the outer epidermal layer. Once inserted these newly intercalated cells expand their apical surface and then they differentiate into specific epidermal cell types. Decreased levels of Dsp resulted in the failure of the radially intercalating cells to expand their apical surface, thereby reducing the number of differentiated multiciliated and secretory cells.Dsp is also required in the development of other ectodermally derived structures such as the mouth, eye and fin that utilize intercalating-like cell movements. We have developed a novel system, in the frog, to demonstrate for the first time that desmosomes not only protect against mechanical stress but are also critical for epidermal morphogenesis.

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“…There, WDR5 stabilizes the actin lattice that allows 30 multiciliated cells to expand their apical surface, pattern basal bodies, and generate hundreds of 31 cilia. 32 33 34 67MCCs remains rudimentary (Sedzinski, et al, 2017;Sedzinski, et al, 2016). Specifically, how 68 the actin lattice architecture is defined and maintained is not understood.…”

mentioning

confidence: 99%

“…MCCs remains rudimentary (Sedzinski, et al, 2017;Sedzinski, et al, 2016). Specifically, how 68 the actin lattice architecture is defined and maintained is not understood.…”

mentioning

confidence: 99%

WDR5 stabilizes actin architecture to promote multiciliated cell formation

Kulkarni

Griffin

Liem

et al. 2017

Preprint

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The actin cytoskeleton is critical to shape cells and pattern intracellular organelles to drive tissue morphogenesis. In multiciliated cells (MCCs), apical actin forms a lattice that drives expansion of the cell surface necessary to host hundreds of cilia. The actin lattice also uniformly distributes basal bodies across this surface. This apical actin network is dynamically remodeled, but the molecules that regulate its architecture remain poorly understood. We identify the chromatin modifier, WDR5, as a regulator of apical F-actin in multiciliated cells. Unexpectedly, WDR5 functions independently of chromatin modification in MCCs. Instead, we discover a scaffolding role for WDR5 between the basal body and F-actin. Specifically, WDR5 binds to basal bodies and migrates apically, where F-actin organizes around WDR5. Using a monomer trap for G-actin, we show that WDR5 stabilizes F-actin to maintain apical lattice architecture. In summary, we identify a novel, non-chromatin role for WDR5 in stabilizing F-actin in multiciliated cells.

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RhoA regulates actin network dynamics during apical surface emergence in multiciliated epithelial cells

Cited by 45 publications

References 48 publications

Regulation of Cilia Abundance in Multiciliated Cells

Regulation of Cilia Abundance in Multiciliated Cells

Desmoplakin is required for epidermal integrity and morphogenesis in theXenopus laevisembryo

WDR5 stabilizes actin architecture to promote multiciliated cell formation

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