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The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance.

Ackley BD, Crew JR, Elamaa H, Pihlajaniemi T, Kuo CJ, Kramer JM - J. Cell Biol. (2001)

Bottom Line: The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system.In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain.These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.

ABSTRACT
Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

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Cell and axon migration defects in cle-1(cg120) animals. Cell and axon positions were analyzed in wild-type (A, C, and E) and cg120 mutant (B, D, and F) animals. Anterior is left, and dorsal is up in all panels. (A and B) HSNs visualized using the tph-1::GFP marker (Sze et al. 2000) are indicated with an arrow. The positions of the vulva (arrowhead) and anus (double arrowhead) are marked to visualize the relative position of the HSN. (A) In wild-type animals, the left HSN is positioned immediately posterior of the vulva. (B) In this cg120 animal, the HSN is displaced posteriorly and dorsally. The HSN axon abnormally projects posteriorly and then ventrally to the ventral cord. (C and D) A panneuronal marker (F25B3.3::GFP) was used to visualize the general organization of the nervous system. (C) In wild-type animals, dorsoventral axon migrations (arrows) follow a trajectory that is orthogonal to the anterior–posterior axis. (D) Axons in cg120 mutants frequently follow nonorthogonal trajectories and defasciculate from one another (arrowheads), but some axon trajectories are normal (arrow). (E and F) Visualization of DA and DB motorneurons using the unc129::GFP reporter. Schematics of the complete DA and DB cell body and axon patterns are shown below, and the area shown in the micrographs is boxed with a dashed line. (E) In wild-type animals, the DA and DB motorneurons extend commissural axons directly from their cell bodies. (F) In this cg120 animal, the DA6 and DB6 axons abnormally migrate anteriorly along the ventral cord, and then both exit on the right side. The DA6 axon should exit on the left side of the ventral cord.
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Figure 4: Cell and axon migration defects in cle-1(cg120) animals. Cell and axon positions were analyzed in wild-type (A, C, and E) and cg120 mutant (B, D, and F) animals. Anterior is left, and dorsal is up in all panels. (A and B) HSNs visualized using the tph-1::GFP marker (Sze et al. 2000) are indicated with an arrow. The positions of the vulva (arrowhead) and anus (double arrowhead) are marked to visualize the relative position of the HSN. (A) In wild-type animals, the left HSN is positioned immediately posterior of the vulva. (B) In this cg120 animal, the HSN is displaced posteriorly and dorsally. The HSN axon abnormally projects posteriorly and then ventrally to the ventral cord. (C and D) A panneuronal marker (F25B3.3::GFP) was used to visualize the general organization of the nervous system. (C) In wild-type animals, dorsoventral axon migrations (arrows) follow a trajectory that is orthogonal to the anterior–posterior axis. (D) Axons in cg120 mutants frequently follow nonorthogonal trajectories and defasciculate from one another (arrowheads), but some axon trajectories are normal (arrow). (E and F) Visualization of DA and DB motorneurons using the unc129::GFP reporter. Schematics of the complete DA and DB cell body and axon patterns are shown below, and the area shown in the micrographs is boxed with a dashed line. (E) In wild-type animals, the DA and DB motorneurons extend commissural axons directly from their cell bodies. (F) In this cg120 animal, the DA6 and DB6 axons abnormally migrate anteriorly along the ventral cord, and then both exit on the right side. The DA6 axon should exit on the left side of the ventral cord.

Mentions: HSN positions were visualized in adults using a tryptophan hydroxylase GFP marker that is expressed in these cells (Sze et al. 2000). In 27% (n = 250) of cg120 animals one or both HSNs were located significantly posterior and/or dorsal of their normal position, suggesting that they failed to complete migration from the tail (Fig. 4 B). HSN axon guidance defects were also observed in cg120 animals but may be secondary effects of cell mispositioning (Baum and Garriga 1997). Animals displaying the Egl phenotype generally had mispositioned HSNs, suggesting that the Egl phenotype results from the HSN migration defect.


The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance.

Ackley BD, Crew JR, Elamaa H, Pihlajaniemi T, Kuo CJ, Kramer JM - J. Cell Biol. (2001)

Cell and axon migration defects in cle-1(cg120) animals. Cell and axon positions were analyzed in wild-type (A, C, and E) and cg120 mutant (B, D, and F) animals. Anterior is left, and dorsal is up in all panels. (A and B) HSNs visualized using the tph-1::GFP marker (Sze et al. 2000) are indicated with an arrow. The positions of the vulva (arrowhead) and anus (double arrowhead) are marked to visualize the relative position of the HSN. (A) In wild-type animals, the left HSN is positioned immediately posterior of the vulva. (B) In this cg120 animal, the HSN is displaced posteriorly and dorsally. The HSN axon abnormally projects posteriorly and then ventrally to the ventral cord. (C and D) A panneuronal marker (F25B3.3::GFP) was used to visualize the general organization of the nervous system. (C) In wild-type animals, dorsoventral axon migrations (arrows) follow a trajectory that is orthogonal to the anterior–posterior axis. (D) Axons in cg120 mutants frequently follow nonorthogonal trajectories and defasciculate from one another (arrowheads), but some axon trajectories are normal (arrow). (E and F) Visualization of DA and DB motorneurons using the unc129::GFP reporter. Schematics of the complete DA and DB cell body and axon patterns are shown below, and the area shown in the micrographs is boxed with a dashed line. (E) In wild-type animals, the DA and DB motorneurons extend commissural axons directly from their cell bodies. (F) In this cg120 animal, the DA6 and DB6 axons abnormally migrate anteriorly along the ventral cord, and then both exit on the right side. The DA6 axon should exit on the left side of the ventral cord.
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Related In: Results  -  Collection

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Figure 4: Cell and axon migration defects in cle-1(cg120) animals. Cell and axon positions were analyzed in wild-type (A, C, and E) and cg120 mutant (B, D, and F) animals. Anterior is left, and dorsal is up in all panels. (A and B) HSNs visualized using the tph-1::GFP marker (Sze et al. 2000) are indicated with an arrow. The positions of the vulva (arrowhead) and anus (double arrowhead) are marked to visualize the relative position of the HSN. (A) In wild-type animals, the left HSN is positioned immediately posterior of the vulva. (B) In this cg120 animal, the HSN is displaced posteriorly and dorsally. The HSN axon abnormally projects posteriorly and then ventrally to the ventral cord. (C and D) A panneuronal marker (F25B3.3::GFP) was used to visualize the general organization of the nervous system. (C) In wild-type animals, dorsoventral axon migrations (arrows) follow a trajectory that is orthogonal to the anterior–posterior axis. (D) Axons in cg120 mutants frequently follow nonorthogonal trajectories and defasciculate from one another (arrowheads), but some axon trajectories are normal (arrow). (E and F) Visualization of DA and DB motorneurons using the unc129::GFP reporter. Schematics of the complete DA and DB cell body and axon patterns are shown below, and the area shown in the micrographs is boxed with a dashed line. (E) In wild-type animals, the DA and DB motorneurons extend commissural axons directly from their cell bodies. (F) In this cg120 animal, the DA6 and DB6 axons abnormally migrate anteriorly along the ventral cord, and then both exit on the right side. The DA6 axon should exit on the left side of the ventral cord.
Mentions: HSN positions were visualized in adults using a tryptophan hydroxylase GFP marker that is expressed in these cells (Sze et al. 2000). In 27% (n = 250) of cg120 animals one or both HSNs were located significantly posterior and/or dorsal of their normal position, suggesting that they failed to complete migration from the tail (Fig. 4 B). HSN axon guidance defects were also observed in cg120 animals but may be secondary effects of cell mispositioning (Baum and Garriga 1997). Animals displaying the Egl phenotype generally had mispositioned HSNs, suggesting that the Egl phenotype results from the HSN migration defect.

Bottom Line: The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system.In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain.These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.

ABSTRACT
Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

Show MeSH
Related in: MedlinePlus