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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 positioning and axon guidance of mechanosensory neurons. The mec-7::GFP marker was used to visualize the anterior (A–D) or posterior (E–F) mechanosensory neuron cell bodies and axons. Anterior is left, and dorsal is up in all panels. (A) In wild-type animals, ALMR (arrow) is located posterior and dorsal of AVM (arrowhead). ALML (*) is out of the plane of focus. (B) In a cg120 mutant, ALMR (arrow) is located anterior of AVM (arrowhead), whereas ALML (*) is normally positioned. (C) In a cg120 animal expressing mec-7::CelNC1, the anterior mechanosensory neurons are normally positioned. (D) In a wild-type animal expressing mec-7::CelES, ALMR (arrow) is located both anterior and ventral of its normal position, whereas ALML is normally positioned. (E and F) PLM cell bodies are not mispositioned in cg120, so their axons were analyzed for guidance defects. (E) In wild-type animals, the PLMR axon (large arrowhead) extends anteriorly along the sublateral tract and terminates just posterior of the ALMR cell body (*). The dorsal edge of the animal is indicated (small arrowheads). (F) In a cg120 animal, the PLMR axon deviates dorsally from the normal ventral sublateral position over a segment of its path (arrows). (G and H) The positions of ALM mechanosensory neurons (G) and canal-associated neurons (CAN; H) were scored in first larval stage animals immediately after hatching using differential interference contrast optics. Cell positions were scored relative to the hypodermal nuclei, which are represented by ovals in the upper part of the drawing. These nuclei are in fixed positions and are used as static markers to score cell positions. Numbers and circles in the lower part of the drawing indicate the percent of animals (n = 50) with cells in the indicated positions.
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Figure 5: Cell positioning and axon guidance of mechanosensory neurons. The mec-7::GFP marker was used to visualize the anterior (A–D) or posterior (E–F) mechanosensory neuron cell bodies and axons. Anterior is left, and dorsal is up in all panels. (A) In wild-type animals, ALMR (arrow) is located posterior and dorsal of AVM (arrowhead). ALML (*) is out of the plane of focus. (B) In a cg120 mutant, ALMR (arrow) is located anterior of AVM (arrowhead), whereas ALML (*) is normally positioned. (C) In a cg120 animal expressing mec-7::CelNC1, the anterior mechanosensory neurons are normally positioned. (D) In a wild-type animal expressing mec-7::CelES, ALMR (arrow) is located both anterior and ventral of its normal position, whereas ALML is normally positioned. (E and F) PLM cell bodies are not mispositioned in cg120, so their axons were analyzed for guidance defects. (E) In wild-type animals, the PLMR axon (large arrowhead) extends anteriorly along the sublateral tract and terminates just posterior of the ALMR cell body (*). The dorsal edge of the animal is indicated (small arrowheads). (F) In a cg120 animal, the PLMR axon deviates dorsally from the normal ventral sublateral position over a segment of its path (arrows). (G and H) The positions of ALM mechanosensory neurons (G) and canal-associated neurons (CAN; H) were scored in first larval stage animals immediately after hatching using differential interference contrast optics. Cell positions were scored relative to the hypodermal nuclei, which are represented by ovals in the upper part of the drawing. These nuclei are in fixed positions and are used as static markers to score cell positions. Numbers and circles in the lower part of the drawing indicate the percent of animals (n = 50) with cells in the indicated positions.

Mentions: In addition to HSNs, other cells that undergo long range migrations during C. elegans development include the anterior mechanosensory neurons (ALML/R and AVM) and the canal-associated neurons. We analyzed these cells for migration defects in cg120 mutants (Fig. 5; Table and Table ). Interestingly, although the canal-associated neuron is the only one of these cells that expresses cle-1, it did not exhibit any migration defects (Fig. 5 J). In 37% (n = 200) of cg120 animals one or more of the mechanosensory neurons were mispositioned (Fig. 5 B; Table ). The ALMs are most often displaced anteriorly, whereas the AVM is displaced posteriorly and/or dorsally. In most cases the cells are mispositioned on the anterior–posterior trajectory along which they normally migrate, although occasionally they are also displaced dorsally or ventrally.


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 positioning and axon guidance of mechanosensory neurons. The mec-7::GFP marker was used to visualize the anterior (A–D) or posterior (E–F) mechanosensory neuron cell bodies and axons. Anterior is left, and dorsal is up in all panels. (A) In wild-type animals, ALMR (arrow) is located posterior and dorsal of AVM (arrowhead). ALML (*) is out of the plane of focus. (B) In a cg120 mutant, ALMR (arrow) is located anterior of AVM (arrowhead), whereas ALML (*) is normally positioned. (C) In a cg120 animal expressing mec-7::CelNC1, the anterior mechanosensory neurons are normally positioned. (D) In a wild-type animal expressing mec-7::CelES, ALMR (arrow) is located both anterior and ventral of its normal position, whereas ALML is normally positioned. (E and F) PLM cell bodies are not mispositioned in cg120, so their axons were analyzed for guidance defects. (E) In wild-type animals, the PLMR axon (large arrowhead) extends anteriorly along the sublateral tract and terminates just posterior of the ALMR cell body (*). The dorsal edge of the animal is indicated (small arrowheads). (F) In a cg120 animal, the PLMR axon deviates dorsally from the normal ventral sublateral position over a segment of its path (arrows). (G and H) The positions of ALM mechanosensory neurons (G) and canal-associated neurons (CAN; H) were scored in first larval stage animals immediately after hatching using differential interference contrast optics. Cell positions were scored relative to the hypodermal nuclei, which are represented by ovals in the upper part of the drawing. These nuclei are in fixed positions and are used as static markers to score cell positions. Numbers and circles in the lower part of the drawing indicate the percent of animals (n = 50) with cells in the indicated positions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199198&req=5

Figure 5: Cell positioning and axon guidance of mechanosensory neurons. The mec-7::GFP marker was used to visualize the anterior (A–D) or posterior (E–F) mechanosensory neuron cell bodies and axons. Anterior is left, and dorsal is up in all panels. (A) In wild-type animals, ALMR (arrow) is located posterior and dorsal of AVM (arrowhead). ALML (*) is out of the plane of focus. (B) In a cg120 mutant, ALMR (arrow) is located anterior of AVM (arrowhead), whereas ALML (*) is normally positioned. (C) In a cg120 animal expressing mec-7::CelNC1, the anterior mechanosensory neurons are normally positioned. (D) In a wild-type animal expressing mec-7::CelES, ALMR (arrow) is located both anterior and ventral of its normal position, whereas ALML is normally positioned. (E and F) PLM cell bodies are not mispositioned in cg120, so their axons were analyzed for guidance defects. (E) In wild-type animals, the PLMR axon (large arrowhead) extends anteriorly along the sublateral tract and terminates just posterior of the ALMR cell body (*). The dorsal edge of the animal is indicated (small arrowheads). (F) In a cg120 animal, the PLMR axon deviates dorsally from the normal ventral sublateral position over a segment of its path (arrows). (G and H) The positions of ALM mechanosensory neurons (G) and canal-associated neurons (CAN; H) were scored in first larval stage animals immediately after hatching using differential interference contrast optics. Cell positions were scored relative to the hypodermal nuclei, which are represented by ovals in the upper part of the drawing. These nuclei are in fixed positions and are used as static markers to score cell positions. Numbers and circles in the lower part of the drawing indicate the percent of animals (n = 50) with cells in the indicated positions.
Mentions: In addition to HSNs, other cells that undergo long range migrations during C. elegans development include the anterior mechanosensory neurons (ALML/R and AVM) and the canal-associated neurons. We analyzed these cells for migration defects in cg120 mutants (Fig. 5; Table and Table ). Interestingly, although the canal-associated neuron is the only one of these cells that expresses cle-1, it did not exhibit any migration defects (Fig. 5 J). In 37% (n = 200) of cg120 animals one or more of the mechanosensory neurons were mispositioned (Fig. 5 B; Table ). The ALMs are most often displaced anteriorly, whereas the AVM is displaced posteriorly and/or dorsally. In most cases the cells are mispositioned on the anterior–posterior trajectory along which they normally migrate, although occasionally they are also displaced dorsally or ventrally.

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