Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity–signaling pathway

Guillabert-Gourgues, Aude; Jaspard-Vinassa, Béatrice; Bats, Marie-Lise; Sewduth, Raj Nayan; Franzl, Nathalie; Peghaire, Claire; Jeanningros, Sylvie; Moreau, Catherine; Roux, Étienne; Larrieu-Lahargue, Frédéric; Dufourcq, Pascale; Couffinhal, Thierry; Duplàa, C.

doi:10.1091/mbc.e14-08-1332

Cited by 34 publications

(32 citation statements)

References 49 publications

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“…Previous investigators have reported that KIF26B localises to microtubules in human endothelial cells. 33 Our data confirm that KIF26B has at least a partial co-localisation with the cytoskeleton in MSCs ( Figure 3F). In silico analysis 34 of a published RNASeq dataset in an in vivo model of ectopic bone formation using human foetal MSCs from an independent study 35 also demonstrated KIF26B induction during osteogenesis ( Figure 3G).…”

Section: Variation Within the Casc20 Locus Is Associated With Ho Suscsupporting

confidence: 82%

Genome-wide association and functional analyses identify CASC20 and KIF26B as target loci in heterotopic ossification

Hatzikotoulas

Pickering

Clark

et al. 2019

Preprint

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Heterotopic ossification (HO) is bone formation that occurs after trauma within tissues that do not normally have the property of ossification, resulting in pain and disability.The genetic architecture of HO remains unclear. In the first genome-wide association studies of this disease, we identify the human-only long non-coding RNA-encoding gene CASC20 as a robust, replicating susceptibility locus for HO and KIF26B as a potential severity locus. We find that both CASC20 and KIF26B are expressed in human bone. Both CASC20 and KIF26B expression is upregulated upon BMP2 induced osteogenic differentiation in primary human mesenchymal stem cells, followed by RUNX2 and OSTERIX upregulation and mineralised nodule formation. A CRISPR-Cas9 mediated knockout of Kif26b inhibits BMP2-induced Runx2, Sp7/Osterix, Col1A1, Alp, and Bglap/Osteocalcin expression in a murine myocyte model of osteogenic trans-differentiation, and prevents mineralised nodule formation. These studies provide the first insights into the heritable biology of common, complex HO.

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Section: Variation Within the Casc20 Locus Is Associated With Ho Suscsupporting

confidence: 82%

Genome-wide association and functional analyses identify CASC20 and KIF26B as target loci in heterotopic ossification

Hatzikotoulas

Pickering

Clark

et al. 2019

Preprint

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“…Sst , Kif26b , Mab21l2 , and Lamp5 mRNAs are also highly enriched and expressed in C‐neurons (Figure h). Sst encodes the hormone Somatostatin (Patel, ); Kif26b encodes a kinesin that regulates cell polarity (Guillabert‐Gourgues et al, ; Marikawa, Fujita, & Alarcon, ); Mab21l2 encodes a nuclear protein that interacts with the BMP4 signaling pathway and has been implicated in neural tube formation and eye morphogenesis (Baldessari, Badaloni, Longhi, Zappavigna, & Consalez, ; Huang, ); Lamp5 encodes a lysosome‐associated membrane protein implicated in GABAergic neurotransmission (Tiveron et al, ). In situ hybridization for these mRNAs in brachial spinal cord transverse sections from E11.5 Robo3 Cre/+ ; ROSA26 LSL‐tdTomato/+ embryos confirmed expression in various subgroups of C‐neurons and revealed additional sites of expression (Figure a–h).…”

Section: Resultsmentioning

confidence: 99%

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse

Tulloch

Teo

Carvajal

et al. 2019

J of Comparative Neurology

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The two sides of the nervous system coordinate and integrate information via commissural neurons, which project axons across the midline. Commissural neurons in the spinal cord are a highly heterogeneous population of cells with respect to their birthplace, final cell body position, axonal trajectory, and neurotransmitter phenotype. Although commissural axon guidance during development has been studied in great detail, neither the developmental origins nor the mature phenotypes of commissural neurons have been characterized comprehensively, largely due to lack of selective genetic access to these neurons. Here, we generated mice expressing Cre recombinase from the Robo3 locus specifically in commissural neurons. We used Robo3 Cre mice to characterize the transcriptome and various origins of developing commissural neurons, revealing new details about their extensive heterogeneity in molecular makeup and developmental lineage. Further, we followed the fate of commissural neurons into adulthood, thereby elucidating their settling positions and molecular diversity and providing evidence for possible functions in various spinal cord circuits. Our studies establish an important genetic entry point for further analyses of commissural neuron development, connectivity, and function.

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“…This could change the balance from a symmetric to an asymmetric MT network and is crucial for proper polarization of cells (Burute et al, 2017). In contrast, in epithelial cells, endothelial cells and mouse airway cilia, regulatory proteins ensure that MTs grow mainly from the apical membrane, rather than from the centrosome (Feldman and Priess, 2012;Vladar et al, 2012;Guillabert-Gourgues et al, 2016;Toya et al, 2016). The result is that MTs grow in parallel bundles instead of a radial conformation, which leads to different transport directions (Fig.…”

Section: Cytoskeleton-based Cell Polaritymentioning

confidence: 99%

Minimal in vitro systems shed light on cell polarity

Vendel

Tschirpke

Shamsi

et al. 2019

Journal of Cell Science

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Cell polaritythe morphological and functional differentiation of cellular compartments in a directional manneris required for processes such as orientation of cell division, directed cellular growth and motility. How the interplay of components within the complexity of a cell leads to cell polarity is still heavily debated. In this Review, we focus on one specific aspect of cell polarity: the non-uniform accumulation of proteins on the cell membrane. In cells, this is achieved through reaction-diffusion and/or cytoskeleton-based mechanisms. In reaction-diffusion systems, components are transformed into each other by chemical reactions and are moving through space by diffusion. In cytoskeleton-based processes, cellular components (i.e. proteins) are actively transported by microtubules (MTs) and actin filaments to specific locations in the cell. We examine how minimal systemsin vitro reconstitutions of a particular cellular function with a minimal number of componentsare designed, how they contribute to our understanding of cell polarity (i.e. protein accumulation), and how they complement in vivo investigations. We start by discussing the Min protein system from Escherichia coli, which represents a reaction-diffusion system with a well-established minimal system. This is followed by a discussion of MT-based directed transport for cell polarity markers as an example of a cytoskeleton-based mechanism. To conclude, we discuss, as an example, the interplay of reaction-diffusion and cytoskeleton-based mechanisms during polarity establishment in budding yeast.

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Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity–signaling pathway

Cited by 34 publications

References 49 publications

Genome-wide association and functional analyses identify CASC20 and KIF26B as target loci in heterotopic ossification

Genome-wide association and functional analyses identify CASC20 and KIF26B as target loci in heterotopic ossification

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse

Minimal in vitro systems shed light on cell polarity

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Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity–signaling pathway

Cited by 34 publications

References 49 publications

Genome-wide association and functional analyses identify CASC20 and KIF26B as target loci in heterotopic ossification

Genome-wide association and functional analyses identify CASC20 and KIF26B as target loci in heterotopic ossification

Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3Cre mouse

Minimal in vitro systems shed light on cell polarity

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Diverse spinal commissural neuron populations revealed by fate mapping and molecular profiling using a novel Robo3^Cre mouse