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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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RNAi against cle-1 results in embryonic and larval lethality. (A–D) Embryonic lethality resulting from RNAi against cle-1. Embryos are oriented with anterior up and ventral to the right. The position of the presumptive oral cavity is indicated by an arrowhead. (A) A wild-type embryo at the 1.5-fold stage of embryogenesis. (B) An embryo arrested at the 1.5–2-fold stage of embryogenesis resulting from RNAi into the wild-type background. The embryo has herniated at the ventral pocket (arrow), which forms during enclosure by the hypodermis. (C and D) Embryos arrested at the 1.5-fold stage of embryogenesis resulting from RNAi into the cg120 background. The embryos are small and misshapen, suggesting defects in hypodermal function. (E and F) Larval lethality resulting from RNAi against cle-1. The posterior bulb of the pharynx is indicated by an arrow, and the anterior bulb by an arrowhead. (E) Wild-type first stage larva. The body has a uniform diameter along its length, and the pharynx lies along the central axis of the animal. (F) Arrested first stage larva resulting from RNAi into the wild type background. The animal is smaller than wild type, and the posterior body is shrunken relative to the anterior. The pharynx is mislocalized laterally and does not pump.
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Figure 7: RNAi against cle-1 results in embryonic and larval lethality. (A–D) Embryonic lethality resulting from RNAi against cle-1. Embryos are oriented with anterior up and ventral to the right. The position of the presumptive oral cavity is indicated by an arrowhead. (A) A wild-type embryo at the 1.5-fold stage of embryogenesis. (B) An embryo arrested at the 1.5–2-fold stage of embryogenesis resulting from RNAi into the wild-type background. The embryo has herniated at the ventral pocket (arrow), which forms during enclosure by the hypodermis. (C and D) Embryos arrested at the 1.5-fold stage of embryogenesis resulting from RNAi into the cg120 background. The embryos are small and misshapen, suggesting defects in hypodermal function. (E and F) Larval lethality resulting from RNAi against cle-1. The posterior bulb of the pharynx is indicated by an arrow, and the anterior bulb by an arrowhead. (E) Wild-type first stage larva. The body has a uniform diameter along its length, and the pharynx lies along the central axis of the animal. (F) Arrested first stage larva resulting from RNAi into the wild type background. The animal is smaller than wild type, and the posterior body is shrunken relative to the anterior. The pharynx is mislocalized laterally and does not pump.

Mentions: Significant levels of both embryonic and larval lethality were seen in offspring from hermaphrodites injected with cle-1-specific dsRNA (Fig. 7; Table ). Embryonic arrest most commonly occurred during early morphogenesis, at approximately the 1.5-fold stage. Larval arrest occurred at the first larval stage, and arrested larvae were small and had misshapen pharynxes that failed to pump. Animals that survived to the adult stage had motorneuron positioning and axon guidance defects (Table ), gonad migration, or male tail defects and were sterile (Table ). These defects are similar to those observed in cg120 mutants. Injection of dsRNA into cg120 mutant animals resulted in higher levels of lethality and sterility (Table ). The occurrence of similar phenotypes, but at higher penetrance in RNAi-treated versus cg120 mutant animals, suggests that RNAi results in greater cle-1 loss-of-function than the cg120 deletion.


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)

RNAi against cle-1 results in embryonic and larval lethality. (A–D) Embryonic lethality resulting from RNAi against cle-1. Embryos are oriented with anterior up and ventral to the right. The position of the presumptive oral cavity is indicated by an arrowhead. (A) A wild-type embryo at the 1.5-fold stage of embryogenesis. (B) An embryo arrested at the 1.5–2-fold stage of embryogenesis resulting from RNAi into the wild-type background. The embryo has herniated at the ventral pocket (arrow), which forms during enclosure by the hypodermis. (C and D) Embryos arrested at the 1.5-fold stage of embryogenesis resulting from RNAi into the cg120 background. The embryos are small and misshapen, suggesting defects in hypodermal function. (E and F) Larval lethality resulting from RNAi against cle-1. The posterior bulb of the pharynx is indicated by an arrow, and the anterior bulb by an arrowhead. (E) Wild-type first stage larva. The body has a uniform diameter along its length, and the pharynx lies along the central axis of the animal. (F) Arrested first stage larva resulting from RNAi into the wild type background. The animal is smaller than wild type, and the posterior body is shrunken relative to the anterior. The pharynx is mislocalized laterally and does not pump.
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Related In: Results  -  Collection

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Figure 7: RNAi against cle-1 results in embryonic and larval lethality. (A–D) Embryonic lethality resulting from RNAi against cle-1. Embryos are oriented with anterior up and ventral to the right. The position of the presumptive oral cavity is indicated by an arrowhead. (A) A wild-type embryo at the 1.5-fold stage of embryogenesis. (B) An embryo arrested at the 1.5–2-fold stage of embryogenesis resulting from RNAi into the wild-type background. The embryo has herniated at the ventral pocket (arrow), which forms during enclosure by the hypodermis. (C and D) Embryos arrested at the 1.5-fold stage of embryogenesis resulting from RNAi into the cg120 background. The embryos are small and misshapen, suggesting defects in hypodermal function. (E and F) Larval lethality resulting from RNAi against cle-1. The posterior bulb of the pharynx is indicated by an arrow, and the anterior bulb by an arrowhead. (E) Wild-type first stage larva. The body has a uniform diameter along its length, and the pharynx lies along the central axis of the animal. (F) Arrested first stage larva resulting from RNAi into the wild type background. The animal is smaller than wild type, and the posterior body is shrunken relative to the anterior. The pharynx is mislocalized laterally and does not pump.
Mentions: Significant levels of both embryonic and larval lethality were seen in offspring from hermaphrodites injected with cle-1-specific dsRNA (Fig. 7; Table ). Embryonic arrest most commonly occurred during early morphogenesis, at approximately the 1.5-fold stage. Larval arrest occurred at the first larval stage, and arrested larvae were small and had misshapen pharynxes that failed to pump. Animals that survived to the adult stage had motorneuron positioning and axon guidance defects (Table ), gonad migration, or male tail defects and were sterile (Table ). These defects are similar to those observed in cg120 mutants. Injection of dsRNA into cg120 mutant animals resulted in higher levels of lethality and sterility (Table ). The occurrence of similar phenotypes, but at higher penetrance in RNAi-treated versus cg120 mutant animals, suggests that RNAi results in greater cle-1 loss-of-function than the cg120 deletion.

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