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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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Male tail and gonad migration defects. Defects in morphogenesis of the male tail (A–C) and the hermaphrodite gonad (D and E), visualized with differential interference contrast microscopy. (A) Ventral view of a wild-type male tail showing the nine bilateral pairs of sensory rays, labeled 1–9, on the left side of the animal. (B) A cg120 male tail shows fusion of rays 8 and 9 (8,9). On the right side, ray 6 is broader than normal, and the cuticle covering it is irregular. (C) The tail of a male ectopically expressing mec-7::CelES shows fusion of rays 1 and 2 (1,2) on both sides of the animal. Ray 6 on the right side (6) appears crumpled, and rays 8 and 9 on the left have fused (8,9). The fans and rays of males expressing mec-7::CelES are smaller than those of wild type. (D) The anterior arm of a wild-type fourth larval stage hermaphrodite gonad. The distal tip cell (DTC) leads gonad migration anteriorly along the dorsal body wall, turns and migrates to the dorsal side, and then migrates posteriorly. The position of the vulva (V) is indicated. A schematic depiction of the DTC migration path is shown to the right of the micrograph. 100% (50/50) of wild-type animals showed this migration pattern. (E) In this cg120 animal, the DTC migrated anteriorly, turned dorsal prematurely while continuing to migrate anteriorly, and then reflexed and migrated posteriorly (dashed line) along the dorsal body wall. The final posterior migration is below the plane of focus. 32% (16/50) of cg120 animals displayed similar migration defects of the anterior gonad. 16% of posterior gonads showed the same defects.
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Figure 6: Male tail and gonad migration defects. Defects in morphogenesis of the male tail (A–C) and the hermaphrodite gonad (D and E), visualized with differential interference contrast microscopy. (A) Ventral view of a wild-type male tail showing the nine bilateral pairs of sensory rays, labeled 1–9, on the left side of the animal. (B) A cg120 male tail shows fusion of rays 8 and 9 (8,9). On the right side, ray 6 is broader than normal, and the cuticle covering it is irregular. (C) The tail of a male ectopically expressing mec-7::CelES shows fusion of rays 1 and 2 (1,2) on both sides of the animal. Ray 6 on the right side (6) appears crumpled, and rays 8 and 9 on the left have fused (8,9). The fans and rays of males expressing mec-7::CelES are smaller than those of wild type. (D) The anterior arm of a wild-type fourth larval stage hermaphrodite gonad. The distal tip cell (DTC) leads gonad migration anteriorly along the dorsal body wall, turns and migrates to the dorsal side, and then migrates posteriorly. The position of the vulva (V) is indicated. A schematic depiction of the DTC migration path is shown to the right of the micrograph. 100% (50/50) of wild-type animals showed this migration pattern. (E) In this cg120 animal, the DTC migrated anteriorly, turned dorsal prematurely while continuing to migrate anteriorly, and then reflexed and migrated posteriorly (dashed line) along the dorsal body wall. The final posterior migration is below the plane of focus. 32% (16/50) of cg120 animals displayed similar migration defects of the anterior gonad. 16% of posterior gonads showed the same defects.

Mentions: cg120 animals also display defects in migrations of nonneuronal cells of the male tail and the hermaphrodite gonad. Formation of the male tail involves complex cell migrations and interactions (Sulston et al. 1980; Emmons 1992). 10% (n = 50) of cg120 males show fusions of sensory rays 1–2 or 7–8–9, and sensory ray 6 is often short and broad (Fig. 6 B). Despite these defects, most cg120 homozygous males can mate. In the hermaphrodite gonad, the most common defect (32%) is a premature dorsal turn of the anterior distal tip cell (Fig. 6 E). The posterior gonad shows similar defects with lower frequency (16%). Gonads are also often slightly shortened relative to wild type, suggesting that the distal tip cells do not migrate completely along the anterior–posterior axis.


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)

Male tail and gonad migration defects. Defects in morphogenesis of the male tail (A–C) and the hermaphrodite gonad (D and E), visualized with differential interference contrast microscopy. (A) Ventral view of a wild-type male tail showing the nine bilateral pairs of sensory rays, labeled 1–9, on the left side of the animal. (B) A cg120 male tail shows fusion of rays 8 and 9 (8,9). On the right side, ray 6 is broader than normal, and the cuticle covering it is irregular. (C) The tail of a male ectopically expressing mec-7::CelES shows fusion of rays 1 and 2 (1,2) on both sides of the animal. Ray 6 on the right side (6) appears crumpled, and rays 8 and 9 on the left have fused (8,9). The fans and rays of males expressing mec-7::CelES are smaller than those of wild type. (D) The anterior arm of a wild-type fourth larval stage hermaphrodite gonad. The distal tip cell (DTC) leads gonad migration anteriorly along the dorsal body wall, turns and migrates to the dorsal side, and then migrates posteriorly. The position of the vulva (V) is indicated. A schematic depiction of the DTC migration path is shown to the right of the micrograph. 100% (50/50) of wild-type animals showed this migration pattern. (E) In this cg120 animal, the DTC migrated anteriorly, turned dorsal prematurely while continuing to migrate anteriorly, and then reflexed and migrated posteriorly (dashed line) along the dorsal body wall. The final posterior migration is below the plane of focus. 32% (16/50) of cg120 animals displayed similar migration defects of the anterior gonad. 16% of posterior gonads showed the same defects.
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Figure 6: Male tail and gonad migration defects. Defects in morphogenesis of the male tail (A–C) and the hermaphrodite gonad (D and E), visualized with differential interference contrast microscopy. (A) Ventral view of a wild-type male tail showing the nine bilateral pairs of sensory rays, labeled 1–9, on the left side of the animal. (B) A cg120 male tail shows fusion of rays 8 and 9 (8,9). On the right side, ray 6 is broader than normal, and the cuticle covering it is irregular. (C) The tail of a male ectopically expressing mec-7::CelES shows fusion of rays 1 and 2 (1,2) on both sides of the animal. Ray 6 on the right side (6) appears crumpled, and rays 8 and 9 on the left have fused (8,9). The fans and rays of males expressing mec-7::CelES are smaller than those of wild type. (D) The anterior arm of a wild-type fourth larval stage hermaphrodite gonad. The distal tip cell (DTC) leads gonad migration anteriorly along the dorsal body wall, turns and migrates to the dorsal side, and then migrates posteriorly. The position of the vulva (V) is indicated. A schematic depiction of the DTC migration path is shown to the right of the micrograph. 100% (50/50) of wild-type animals showed this migration pattern. (E) In this cg120 animal, the DTC migrated anteriorly, turned dorsal prematurely while continuing to migrate anteriorly, and then reflexed and migrated posteriorly (dashed line) along the dorsal body wall. The final posterior migration is below the plane of focus. 32% (16/50) of cg120 animals displayed similar migration defects of the anterior gonad. 16% of posterior gonads showed the same defects.
Mentions: cg120 animals also display defects in migrations of nonneuronal cells of the male tail and the hermaphrodite gonad. Formation of the male tail involves complex cell migrations and interactions (Sulston et al. 1980; Emmons 1992). 10% (n = 50) of cg120 males show fusions of sensory rays 1–2 or 7–8–9, and sensory ray 6 is often short and broad (Fig. 6 B). Despite these defects, most cg120 homozygous males can mate. In the hermaphrodite gonad, the most common defect (32%) is a premature dorsal turn of the anterior distal tip cell (Fig. 6 E). The posterior gonad shows similar defects with lower frequency (16%). Gonads are also often slightly shortened relative to wild type, suggesting that the distal tip cells do not migrate completely along the anterior–posterior axis.

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