Limits...
LAD-1, the Caenorhabditis elegans L1CAM homologue, participates in embryonic and gonadal morphogenesis and is a substrate for fibroblast growth factor receptor pathway-dependent phosphotyrosine-based signaling.

Chen L, Ong B, Bennett V - J. Cell Biol. (2001)

Bottom Line: In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell-cell contact.These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling.Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Cell Biology, and Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. l.chen@cellbio.duke.edu

ABSTRACT
This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis elegans homologue of the L1 family of neuronal adhesion molecules, is required for proper development of the germline and the early embryo and embryonic and gonadal morphogenesis. In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell-cell contact. Finally, we show that LAD-1 is phosphorylated in a fibroblast growth factor receptor (FGFR) pathway-dependent manner on a tyrosine residue in the highly conserved ankyrin-binding motif, FIGQY, which was shown previously to abolish the L1 family of cell adhesion molecule (L1CAM) binding to ankyrin in cultured cells. Immunofluorescence studies revealed that FIGQY-tyrosine-phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead is localized to sites that undergo mechanical stress in polarized epithelia and axon-body wall muscle junctions. These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling. Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.

Show MeSH

Related in: MedlinePlus

LAD-1 plays a role in embryonic morphogenesis and in germline and early embryo development. (A) Transgenic animals expressing a dominant negative form of LAD-1 display morphogenetic defects: anterior Vabs (i) and posterior Vabs (ii) (a, anterior; p, posterior). Wild-type animals are shown in iii and iv. (B) Apparent cell adhesion defects between oocytes result in mispositioned and misshapen oocytes, (i, arrows, and iii, short arrow). In addition, misplaced germ cells and immature-looking oocytes were detected (iii, long arrows). Apparent cell adhesion defects in early embryos result in misshapen cells and embryos, indicated by arrows in ii, that have yet to be laid through the vulva as designated by the arrowhead. The wild-type germline is displayed in iv, showing normal germline nuclei (long arrows), properly shaped and positioned oocytes (short arrows), and wild-type embryos (mid-sized arrows). Bar, 25 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196473&req=5

fig9: LAD-1 plays a role in embryonic morphogenesis and in germline and early embryo development. (A) Transgenic animals expressing a dominant negative form of LAD-1 display morphogenetic defects: anterior Vabs (i) and posterior Vabs (ii) (a, anterior; p, posterior). Wild-type animals are shown in iii and iv. (B) Apparent cell adhesion defects between oocytes result in mispositioned and misshapen oocytes, (i, arrows, and iii, short arrow). In addition, misplaced germ cells and immature-looking oocytes were detected (iii, long arrows). Apparent cell adhesion defects in early embryos result in misshapen cells and embryos, indicated by arrows in ii, that have yet to be laid through the vulva as designated by the arrowhead. The wild-type germline is displayed in iv, showing normal germline nuclei (long arrows), properly shaped and positioned oocytes (short arrows), and wild-type embryos (mid-sized arrows). Bar, 25 μm.

Mentions: Dominant negative LAD-1 transgenic animals displayed pleiotropic phenotypes. 57% of the transgenic animals were variable abnormal (Vabs) (Fig. 9, A , i and ii), which indicates morphogenic defects, 34% showed uncoordinated movements and variable lethality, and 40% showed defects in gonadal morphogenesis. Striking defects in germline and early embryonic development were also observed. In the wild-type germline (Fig. 9, B, iv), embryos are situated close to the vulva (mid-sized arrows), and the oocytes are lined up in the proximal gonad (short arrows), whereas meiotic germline nuclei are located more distally (long arrows). Loss of contact between oocytes was observed in these transgenic animals, resulting in oocytes with altered shapes and sizes (Fig. 9, B, i and iii). In addition, many germ cell nuclei were completely enclosed by a membrane (Fig. 9, B, iii, long arrows), suggesting the presence of premature oocytes. Many dominant negative LAD-1 transgenic embryos also had cells with altered shapes and positions (Fig. 9, B, ii). In the early C. elegans embryos, the invariant cell position is critical for proper embryogenesis, due to cell–cell signaling (Schnabel and Priess, 1997). Because of the apparent loss of cell contact in these transgenic embryos, many of these embryos did not complete embryogenesis.


LAD-1, the Caenorhabditis elegans L1CAM homologue, participates in embryonic and gonadal morphogenesis and is a substrate for fibroblast growth factor receptor pathway-dependent phosphotyrosine-based signaling.

Chen L, Ong B, Bennett V - J. Cell Biol. (2001)

LAD-1 plays a role in embryonic morphogenesis and in germline and early embryo development. (A) Transgenic animals expressing a dominant negative form of LAD-1 display morphogenetic defects: anterior Vabs (i) and posterior Vabs (ii) (a, anterior; p, posterior). Wild-type animals are shown in iii and iv. (B) Apparent cell adhesion defects between oocytes result in mispositioned and misshapen oocytes, (i, arrows, and iii, short arrow). In addition, misplaced germ cells and immature-looking oocytes were detected (iii, long arrows). Apparent cell adhesion defects in early embryos result in misshapen cells and embryos, indicated by arrows in ii, that have yet to be laid through the vulva as designated by the arrowhead. The wild-type germline is displayed in iv, showing normal germline nuclei (long arrows), properly shaped and positioned oocytes (short arrows), and wild-type embryos (mid-sized arrows). Bar, 25 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196473&req=5

fig9: LAD-1 plays a role in embryonic morphogenesis and in germline and early embryo development. (A) Transgenic animals expressing a dominant negative form of LAD-1 display morphogenetic defects: anterior Vabs (i) and posterior Vabs (ii) (a, anterior; p, posterior). Wild-type animals are shown in iii and iv. (B) Apparent cell adhesion defects between oocytes result in mispositioned and misshapen oocytes, (i, arrows, and iii, short arrow). In addition, misplaced germ cells and immature-looking oocytes were detected (iii, long arrows). Apparent cell adhesion defects in early embryos result in misshapen cells and embryos, indicated by arrows in ii, that have yet to be laid through the vulva as designated by the arrowhead. The wild-type germline is displayed in iv, showing normal germline nuclei (long arrows), properly shaped and positioned oocytes (short arrows), and wild-type embryos (mid-sized arrows). Bar, 25 μm.
Mentions: Dominant negative LAD-1 transgenic animals displayed pleiotropic phenotypes. 57% of the transgenic animals were variable abnormal (Vabs) (Fig. 9, A , i and ii), which indicates morphogenic defects, 34% showed uncoordinated movements and variable lethality, and 40% showed defects in gonadal morphogenesis. Striking defects in germline and early embryonic development were also observed. In the wild-type germline (Fig. 9, B, iv), embryos are situated close to the vulva (mid-sized arrows), and the oocytes are lined up in the proximal gonad (short arrows), whereas meiotic germline nuclei are located more distally (long arrows). Loss of contact between oocytes was observed in these transgenic animals, resulting in oocytes with altered shapes and sizes (Fig. 9, B, i and iii). In addition, many germ cell nuclei were completely enclosed by a membrane (Fig. 9, B, iii, long arrows), suggesting the presence of premature oocytes. Many dominant negative LAD-1 transgenic embryos also had cells with altered shapes and positions (Fig. 9, B, ii). In the early C. elegans embryos, the invariant cell position is critical for proper embryogenesis, due to cell–cell signaling (Schnabel and Priess, 1997). Because of the apparent loss of cell contact in these transgenic embryos, many of these embryos did not complete embryogenesis.

Bottom Line: In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell-cell contact.These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling.Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Department of Cell Biology, and Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. l.chen@cellbio.duke.edu

ABSTRACT
This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis elegans homologue of the L1 family of neuronal adhesion molecules, is required for proper development of the germline and the early embryo and embryonic and gonadal morphogenesis. In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell-cell contact. Finally, we show that LAD-1 is phosphorylated in a fibroblast growth factor receptor (FGFR) pathway-dependent manner on a tyrosine residue in the highly conserved ankyrin-binding motif, FIGQY, which was shown previously to abolish the L1 family of cell adhesion molecule (L1CAM) binding to ankyrin in cultured cells. Immunofluorescence studies revealed that FIGQY-tyrosine-phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead is localized to sites that undergo mechanical stress in polarized epithelia and axon-body wall muscle junctions. These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling. Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.

Show MeSH
Related in: MedlinePlus