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Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning.

Song H, Hu J, Chen W, Elliott G, Andre P, Gao B, Yang Y - Nature (2010)

Bottom Line: We show that PCP is essential in interpreting the A-P patterning information and linking it to L-R asymmetry.PCP in mouse, unlike what has been implicated in other vertebrate species, is not required for ciliogenesis, cilium motility, Sonic hedgehog (Shh) signalling or apical docking of basal bodies in ciliated tracheal epithelial cells.Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development.

View Article: PubMed Central - PubMed

Affiliation: Developmental Genetics Section, Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.

ABSTRACT
Defining the three body axes is a central event of vertebrate morphogenesis. Establishment of left-right (L-R) asymmetry in development follows the determination of dorsal-ventral and anterior-posterior (A-P) body axes, although the molecular mechanism underlying precise L-R symmetry breaking in reference to the other two axes is still poorly understood. Here, by removing both Vangl1 and Vangl2, the two mouse homologues of a Drosophila core planar cell polarity (PCP) gene Van Gogh (Vang), we reveal a previously unrecognized function of PCP in the initial breaking of lateral symmetry. The leftward nodal flow across the posterior notochord (PNC) has been identified as the earliest event in the de novo formation of L-R asymmetry. We show that PCP is essential in interpreting the A-P patterning information and linking it to L-R asymmetry. In the absence of Vangl1 and Vangl2, cilia are positioned randomly around the centre of the PNC cells and nodal flow is turbulent, which results in disrupted L-R asymmetry. PCP in mouse, unlike what has been implicated in other vertebrate species, is not required for ciliogenesis, cilium motility, Sonic hedgehog (Shh) signalling or apical docking of basal bodies in ciliated tracheal epithelial cells. Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development.

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The Vangl2Δ/Δ; Vangl1gt/gt embryos exhibit the most severe polarity defectsa, Asymmetrical localization of Vangl1 protein (green) in the sensory hair cells of the Vangl2Δ/Δ cochlea at E18.5. b, The sensory hair cell polarity at E18.5 is shown by the orientation of actin-based stereocilium bundles (red) and the microtubule-based kinocilia (green). c, Quantification of misoriented hair cells in embryos with different genotypes. Data are means ±SD from 3 samples. The orientation defects in the cochlea ranged from few misoriented cells (Vangl2Δ/+;Vangl1gt/gt) to several affected cells (Vangl2Δ/Δ, Vangl2Lp/+;Vangl1gt/gt and Vangl2 Lp̃Lp) to almost complete loss of polarity (Vangl2Δ/Δ; Vangl1gt/gt).
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Figure 1: The Vangl2Δ/Δ; Vangl1gt/gt embryos exhibit the most severe polarity defectsa, Asymmetrical localization of Vangl1 protein (green) in the sensory hair cells of the Vangl2Δ/Δ cochlea at E18.5. b, The sensory hair cell polarity at E18.5 is shown by the orientation of actin-based stereocilium bundles (red) and the microtubule-based kinocilia (green). c, Quantification of misoriented hair cells in embryos with different genotypes. Data are means ±SD from 3 samples. The orientation defects in the cochlea ranged from few misoriented cells (Vangl2Δ/+;Vangl1gt/gt) to several affected cells (Vangl2Δ/Δ, Vangl2Lp/+;Vangl1gt/gt and Vangl2 Lp̃Lp) to almost complete loss of polarity (Vangl2Δ/Δ; Vangl1gt/gt).

Mentions: A bona fide allele of Vangl1 (Vangl1gt) was generated using a gene trap ES cell line (Supplementary Fig. 3). We also generated a floxed Vangl2 allele, Vangl2f, from which the Vangl2Δ allele was derived (Supplementary Fig. 3). Vangl1 and Vangl2 regulated PCP in a gene dose-dependent manner (Fig. 1 and Supplementary Fig. 4). In the cochlea of the Vangl2Δ/Δ mutant, asymmetrical Vangl1 localization was still detected (Fig. 1a). The Vangl2Δ/Δ; Vangl1gt/gt embryos showed the most severe developmental defects compared to embryos with other genotypes, particularly when sensory hair cell polarity and CE were examined to assess PCP. Thus, Vangl1 and Vangl2 function of regulating PCP was removed in the Vangl2Δ/Δ; Vangl1gt/gt embryos.


Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning.

Song H, Hu J, Chen W, Elliott G, Andre P, Gao B, Yang Y - Nature (2010)

The Vangl2Δ/Δ; Vangl1gt/gt embryos exhibit the most severe polarity defectsa, Asymmetrical localization of Vangl1 protein (green) in the sensory hair cells of the Vangl2Δ/Δ cochlea at E18.5. b, The sensory hair cell polarity at E18.5 is shown by the orientation of actin-based stereocilium bundles (red) and the microtubule-based kinocilia (green). c, Quantification of misoriented hair cells in embryos with different genotypes. Data are means ±SD from 3 samples. The orientation defects in the cochlea ranged from few misoriented cells (Vangl2Δ/+;Vangl1gt/gt) to several affected cells (Vangl2Δ/Δ, Vangl2Lp/+;Vangl1gt/gt and Vangl2 Lp̃Lp) to almost complete loss of polarity (Vangl2Δ/Δ; Vangl1gt/gt).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065171&req=5

Figure 1: The Vangl2Δ/Δ; Vangl1gt/gt embryos exhibit the most severe polarity defectsa, Asymmetrical localization of Vangl1 protein (green) in the sensory hair cells of the Vangl2Δ/Δ cochlea at E18.5. b, The sensory hair cell polarity at E18.5 is shown by the orientation of actin-based stereocilium bundles (red) and the microtubule-based kinocilia (green). c, Quantification of misoriented hair cells in embryos with different genotypes. Data are means ±SD from 3 samples. The orientation defects in the cochlea ranged from few misoriented cells (Vangl2Δ/+;Vangl1gt/gt) to several affected cells (Vangl2Δ/Δ, Vangl2Lp/+;Vangl1gt/gt and Vangl2 Lp̃Lp) to almost complete loss of polarity (Vangl2Δ/Δ; Vangl1gt/gt).
Mentions: A bona fide allele of Vangl1 (Vangl1gt) was generated using a gene trap ES cell line (Supplementary Fig. 3). We also generated a floxed Vangl2 allele, Vangl2f, from which the Vangl2Δ allele was derived (Supplementary Fig. 3). Vangl1 and Vangl2 regulated PCP in a gene dose-dependent manner (Fig. 1 and Supplementary Fig. 4). In the cochlea of the Vangl2Δ/Δ mutant, asymmetrical Vangl1 localization was still detected (Fig. 1a). The Vangl2Δ/Δ; Vangl1gt/gt embryos showed the most severe developmental defects compared to embryos with other genotypes, particularly when sensory hair cell polarity and CE were examined to assess PCP. Thus, Vangl1 and Vangl2 function of regulating PCP was removed in the Vangl2Δ/Δ; Vangl1gt/gt embryos.

Bottom Line: We show that PCP is essential in interpreting the A-P patterning information and linking it to L-R asymmetry.PCP in mouse, unlike what has been implicated in other vertebrate species, is not required for ciliogenesis, cilium motility, Sonic hedgehog (Shh) signalling or apical docking of basal bodies in ciliated tracheal epithelial cells.Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development.

View Article: PubMed Central - PubMed

Affiliation: Developmental Genetics Section, Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.

ABSTRACT
Defining the three body axes is a central event of vertebrate morphogenesis. Establishment of left-right (L-R) asymmetry in development follows the determination of dorsal-ventral and anterior-posterior (A-P) body axes, although the molecular mechanism underlying precise L-R symmetry breaking in reference to the other two axes is still poorly understood. Here, by removing both Vangl1 and Vangl2, the two mouse homologues of a Drosophila core planar cell polarity (PCP) gene Van Gogh (Vang), we reveal a previously unrecognized function of PCP in the initial breaking of lateral symmetry. The leftward nodal flow across the posterior notochord (PNC) has been identified as the earliest event in the de novo formation of L-R asymmetry. We show that PCP is essential in interpreting the A-P patterning information and linking it to L-R asymmetry. In the absence of Vangl1 and Vangl2, cilia are positioned randomly around the centre of the PNC cells and nodal flow is turbulent, which results in disrupted L-R asymmetry. PCP in mouse, unlike what has been implicated in other vertebrate species, is not required for ciliogenesis, cilium motility, Sonic hedgehog (Shh) signalling or apical docking of basal bodies in ciliated tracheal epithelial cells. Our data suggest that PCP acts earlier than the unidirectional nodal flow during bilateral symmetry breaking in vertebrates and provide insight into the functional mechanism of PCP in organizing the vertebrate tissues in development.

Show MeSH
Related in: MedlinePlus