Limits...
Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles.

Devenport D, Fuchs E - Nat. Cell Biol. (2008)

Bottom Line: Moreover, loss-of-function mutations in Vangl2 and Celsr1 show that they have an essential role in hair follicle polarization and orientation, which develop in part through non-autonomous mechanisms.Vangl2 and Celsr1 are both required for their planar localization in vivo, and physically associate in a complex in vitro.Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, New York, NY 10065, USA.

ABSTRACT
Mammalian body hairs align along the anterior-posterior (A-P) axis and offer a striking but poorly understood example of global cell polarization, a phenomenon known as planar cell polarity (PCP). We have discovered that during embryogenesis, marked changes in cell shape and cytoskeletal polarization occur as nascent hair follicles become anteriorly angled, morphologically polarized and molecularly compartmentalized along the A-P axis. Hair follicle initiation coincides with asymmetric redistribution of Vangl2, Celsr1 and Fzd6 within the embryonic epidermal basal layer. Moreover, loss-of-function mutations in Vangl2 and Celsr1 show that they have an essential role in hair follicle polarization and orientation, which develop in part through non-autonomous mechanisms. Vangl2 and Celsr1 are both required for their planar localization in vivo, and physically associate in a complex in vitro. Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact.

Show MeSH

Related in: MedlinePlus

Loss of hair follicle asymmetry in PCP mutants(a–p). Immunofluorescence microscopy of planar (c,d) or sagittal (rest) confocal skin sections from WT or Lp/Lp mutant embryos labelled with Abs or epifluorescence as indicated. (a–b) Anterior cells near the top of Lp/Lp follicles (E16.5) no longer constrict basally (arrowheads). (c–d) Loss of anterior-posterior asymmetry in architecture of Lp/Lp hair germs (E15.5). (e–f) E16.5 WT and Lp/Lp embryos on transgenic background of K14-GFPactin. Note that the apical enrichment (arrows) and basal constrictions (arrowheads) of F-actin are lost at the anterior-posterior junctions between Lp/Lp hair germs and epidermis. (g–h) The asymmetric distribution of keratin 5 (K5) positive protrusions, typically on the anterior side of WT hair pegs at E18.5, is replaced by smaller K5-positive protrusions on both sides of Lp mutant hair pegs (arrowheads). (i–p) Intercellular adhesion proteins are no longer asymmetrically distributed within the anterior and posterior sides of hair germs in E17.5 Lp/Lp embryos. (q–q’) Chimeric embryos (E16.5) were generated from blastocysts composed of WT and Lp/Lp cells (see Experimental Procedures). WT cells are indicated by (+) symbols and are marked by the presence of Vangl2; Lp/Lp mutant cells are denoted by (−) symbols and marked by the absence of cell border Vangl2 staining (q). Note that despite consisting almost entirely of WT cells, HFs from chimeric mice fail to asymmetrically express NCAM (q’; green), or point towards the anterior when surrounded by Lp/Lp mutant interfollicular epidermal cells. Scale bars 10µm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2607065&req=5

Figure 6: Loss of hair follicle asymmetry in PCP mutants(a–p). Immunofluorescence microscopy of planar (c,d) or sagittal (rest) confocal skin sections from WT or Lp/Lp mutant embryos labelled with Abs or epifluorescence as indicated. (a–b) Anterior cells near the top of Lp/Lp follicles (E16.5) no longer constrict basally (arrowheads). (c–d) Loss of anterior-posterior asymmetry in architecture of Lp/Lp hair germs (E15.5). (e–f) E16.5 WT and Lp/Lp embryos on transgenic background of K14-GFPactin. Note that the apical enrichment (arrows) and basal constrictions (arrowheads) of F-actin are lost at the anterior-posterior junctions between Lp/Lp hair germs and epidermis. (g–h) The asymmetric distribution of keratin 5 (K5) positive protrusions, typically on the anterior side of WT hair pegs at E18.5, is replaced by smaller K5-positive protrusions on both sides of Lp mutant hair pegs (arrowheads). (i–p) Intercellular adhesion proteins are no longer asymmetrically distributed within the anterior and posterior sides of hair germs in E17.5 Lp/Lp embryos. (q–q’) Chimeric embryos (E16.5) were generated from blastocysts composed of WT and Lp/Lp cells (see Experimental Procedures). WT cells are indicated by (+) symbols and are marked by the presence of Vangl2; Lp/Lp mutant cells are denoted by (−) symbols and marked by the absence of cell border Vangl2 staining (q). Note that despite consisting almost entirely of WT cells, HFs from chimeric mice fail to asymmetrically express NCAM (q’; green), or point towards the anterior when surrounded by Lp/Lp mutant interfollicular epidermal cells. Scale bars 10µm.

Mentions: The orientation defect in Lp and Crsh mutant follicles suggested that individual HFs might have lost A–P polarization. Indeed several polarized features were lost in Lp/Lp and Crsh/Crsh mutant hair germs: 1) anterior germ cells adjacent to epidermis failed to constrict basally (Fig. 6a–b; Fig. S4a); 2) viewed dorsally, mutant germs appeared circular (Fig. 6c–d; Fig. S4b); 3) GFPactin failed to accumulate basally in anterior germ cells, while gaps in cortical actin formed in central germ cells (Fig. 6e–f); 4) basal keratin protrusions, normally found anteriorly, were found on both sides of mutant follicles (Fig. 6g–h; Fig. S4c).


Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles.

Devenport D, Fuchs E - Nat. Cell Biol. (2008)

Loss of hair follicle asymmetry in PCP mutants(a–p). Immunofluorescence microscopy of planar (c,d) or sagittal (rest) confocal skin sections from WT or Lp/Lp mutant embryos labelled with Abs or epifluorescence as indicated. (a–b) Anterior cells near the top of Lp/Lp follicles (E16.5) no longer constrict basally (arrowheads). (c–d) Loss of anterior-posterior asymmetry in architecture of Lp/Lp hair germs (E15.5). (e–f) E16.5 WT and Lp/Lp embryos on transgenic background of K14-GFPactin. Note that the apical enrichment (arrows) and basal constrictions (arrowheads) of F-actin are lost at the anterior-posterior junctions between Lp/Lp hair germs and epidermis. (g–h) The asymmetric distribution of keratin 5 (K5) positive protrusions, typically on the anterior side of WT hair pegs at E18.5, is replaced by smaller K5-positive protrusions on both sides of Lp mutant hair pegs (arrowheads). (i–p) Intercellular adhesion proteins are no longer asymmetrically distributed within the anterior and posterior sides of hair germs in E17.5 Lp/Lp embryos. (q–q’) Chimeric embryos (E16.5) were generated from blastocysts composed of WT and Lp/Lp cells (see Experimental Procedures). WT cells are indicated by (+) symbols and are marked by the presence of Vangl2; Lp/Lp mutant cells are denoted by (−) symbols and marked by the absence of cell border Vangl2 staining (q). Note that despite consisting almost entirely of WT cells, HFs from chimeric mice fail to asymmetrically express NCAM (q’; green), or point towards the anterior when surrounded by Lp/Lp mutant interfollicular epidermal cells. Scale bars 10µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2607065&req=5

Figure 6: Loss of hair follicle asymmetry in PCP mutants(a–p). Immunofluorescence microscopy of planar (c,d) or sagittal (rest) confocal skin sections from WT or Lp/Lp mutant embryos labelled with Abs or epifluorescence as indicated. (a–b) Anterior cells near the top of Lp/Lp follicles (E16.5) no longer constrict basally (arrowheads). (c–d) Loss of anterior-posterior asymmetry in architecture of Lp/Lp hair germs (E15.5). (e–f) E16.5 WT and Lp/Lp embryos on transgenic background of K14-GFPactin. Note that the apical enrichment (arrows) and basal constrictions (arrowheads) of F-actin are lost at the anterior-posterior junctions between Lp/Lp hair germs and epidermis. (g–h) The asymmetric distribution of keratin 5 (K5) positive protrusions, typically on the anterior side of WT hair pegs at E18.5, is replaced by smaller K5-positive protrusions on both sides of Lp mutant hair pegs (arrowheads). (i–p) Intercellular adhesion proteins are no longer asymmetrically distributed within the anterior and posterior sides of hair germs in E17.5 Lp/Lp embryos. (q–q’) Chimeric embryos (E16.5) were generated from blastocysts composed of WT and Lp/Lp cells (see Experimental Procedures). WT cells are indicated by (+) symbols and are marked by the presence of Vangl2; Lp/Lp mutant cells are denoted by (−) symbols and marked by the absence of cell border Vangl2 staining (q). Note that despite consisting almost entirely of WT cells, HFs from chimeric mice fail to asymmetrically express NCAM (q’; green), or point towards the anterior when surrounded by Lp/Lp mutant interfollicular epidermal cells. Scale bars 10µm.
Mentions: The orientation defect in Lp and Crsh mutant follicles suggested that individual HFs might have lost A–P polarization. Indeed several polarized features were lost in Lp/Lp and Crsh/Crsh mutant hair germs: 1) anterior germ cells adjacent to epidermis failed to constrict basally (Fig. 6a–b; Fig. S4a); 2) viewed dorsally, mutant germs appeared circular (Fig. 6c–d; Fig. S4b); 3) GFPactin failed to accumulate basally in anterior germ cells, while gaps in cortical actin formed in central germ cells (Fig. 6e–f); 4) basal keratin protrusions, normally found anteriorly, were found on both sides of mutant follicles (Fig. 6g–h; Fig. S4c).

Bottom Line: Moreover, loss-of-function mutations in Vangl2 and Celsr1 show that they have an essential role in hair follicle polarization and orientation, which develop in part through non-autonomous mechanisms.Vangl2 and Celsr1 are both required for their planar localization in vivo, and physically associate in a complex in vitro.Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, New York, NY 10065, USA.

ABSTRACT
Mammalian body hairs align along the anterior-posterior (A-P) axis and offer a striking but poorly understood example of global cell polarization, a phenomenon known as planar cell polarity (PCP). We have discovered that during embryogenesis, marked changes in cell shape and cytoskeletal polarization occur as nascent hair follicles become anteriorly angled, morphologically polarized and molecularly compartmentalized along the A-P axis. Hair follicle initiation coincides with asymmetric redistribution of Vangl2, Celsr1 and Fzd6 within the embryonic epidermal basal layer. Moreover, loss-of-function mutations in Vangl2 and Celsr1 show that they have an essential role in hair follicle polarization and orientation, which develop in part through non-autonomous mechanisms. Vangl2 and Celsr1 are both required for their planar localization in vivo, and physically associate in a complex in vitro. Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact.

Show MeSH
Related in: MedlinePlus